TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Slađana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4662547
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6648
AB  - Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
DO  - 10.1016/j.bmc.2024.117649
SP  - 117649
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6648
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Slađana V. and Andrić, Deana and Penjišević, Jelena Z.",
year = "2024",
abstract = "Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
doi = "10.1016/j.bmc.2024.117649",
pages = "117649",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6648"
}

Jevtić, I. I., Suručić, R. V., Tovilović-Kovačević, G., Zogović, N., Kostić-Rajačić, S. V., Andrić, D.,& Penjišević, J. Z.. (2024). Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 101, 117649.
https://doi.org/10.1016/j.bmc.2024.117649
https://hdl.handle.net/21.15107/rcub_ibiss_6648

Jevtić II, Suručić RV, Tovilović-Kovačević G, Zogović N, Kostić-Rajačić SV, Andrić D, Penjišević JZ. Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry. 2024;101:117649.
doi:10.1016/j.bmc.2024.117649
https://hdl.handle.net/21.15107/rcub_ibiss_6648 .

Jevtić, Ivana I., Suručić, Relja V., Tovilović-Kovačević, Gordana, Zogović, Nevena, Kostić-Rajačić, Slađana V., Andrić, Deana, Penjišević, Jelena Z., "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study" in Bioorganic & Medicinal Chemistry, 101 (2024):117649,
https://doi.org/10.1016/j.bmc.2024.117649 .,
https://hdl.handle.net/21.15107/rcub_ibiss_6648 .

TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Suručić, Relja V.
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Kostić-Rajačić, Slađana V.
AU  - Andrić, Deana
AU  - Penjišević, Jelena Z.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6629
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4662547
AB  - Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.
PB  - Amsterdam: Elsevier Ltd
T2  - Bioorganic & Medicinal Chemistry
T1  - Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
VL  - 101
DO  - 10.1016/j.bmc.2024.117649
SP  - 117649
ER  - 

@article{
author = "Jevtić, Ivana I. and Suručić, Relja V. and Tovilović-Kovačević, Gordana and Zogović, Nevena and Kostić-Rajačić, Slađana V. and Andrić, Deana and Penjišević, Jelena Z.",
year = "2024",
abstract = "Simple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from 117.5 to 455 nM for AChE and 34 to 324 nM for BuChE. As a representative of the series with the best cytotoxicity / ChE inhibitory activity ratio, expressed as the selectivity index (SI), 2-chlorobenzoyl derivative demonstrated mixed-type inhibition on AChE and BuChE, suggesting binding to both CAS and PAS of the enzymes. It also exhibited antioxidant capacity and neuroprotective potential against amyloid-β (Aβ) toxicity in the culture of neuron-like cells. In-depth computational analysis corroborated well with in vitro ChE inhibition, illuminating that all compounds exhibit significant potential in targeting both enzymes. Molecular dynamics (MD) simulations revealed that 2-chlorobenzoyl derivative, created complexes with AChE and BuChE that demonstrated sufficient stability throughout the observed MD simulation. Computationally predicted ADME properties indicated that these compounds should have good blood–brain barrier (BBB) permeability, an important factor for CNS-targeting drugs. Overall, all tested compounds showed promising pharmacological behavior, highlighting the multi-target potential of 2- chlorobenzoyl derivative which should be further investigated as a new lead in the drug development process.",
publisher = "Amsterdam: Elsevier Ltd",
journal = "Bioorganic & Medicinal Chemistry",
title = "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study",
volume = "101",
doi = "10.1016/j.bmc.2024.117649",
pages = "117649"
}

Jevtić, I. I., Suručić, R. V., Tovilović-Kovačević, G., Zogović, N., Kostić-Rajačić, S. V., Andrić, D.,& Penjišević, J. Z.. (2024). Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry
Amsterdam: Elsevier Ltd., 101, 117649.
https://doi.org/10.1016/j.bmc.2024.117649

Jevtić II, Suručić RV, Tovilović-Kovačević G, Zogović N, Kostić-Rajačić SV, Andrić D, Penjišević JZ. Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study. in Bioorganic & Medicinal Chemistry. 2024;101:117649.
doi:10.1016/j.bmc.2024.117649 .

Jevtić, Ivana I., Suručić, Relja V., Tovilović-Kovačević, Gordana, Zogović, Nevena, Kostić-Rajačić, Slađana V., Andrić, Deana, Penjišević, Jelena Z., "Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study" in Bioorganic & Medicinal Chemistry, 101 (2024):117649,
https://doi.org/10.1016/j.bmc.2024.117649 . .

TY  - CONF
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Paunović, Verica
AU  - Bošnjak, Mihajlo
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://indico.bio.bg.ac.rs/event/4/attachments/6/492/Abstract%20Book-CoMBoS2-TMB.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6284
AB  - Introduction: We examined the molecular mechanisms of graphene quantum dot (GQD)- mediated
protection of SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
Methods: GQD was produced by electrochemical oxidation of graphite and characterized by AFM, UVVIS and FTIR spectroscopy. The antioxidant activity of GQD in cell-free conditions was assessed by DPPH,
NBT and EPR analysis. The neuroprotective potential of GQD was determined by cell viability assays MTT,
CV. Flow cytometry was used to assess markers of apoptosis and GQD scavenging of intracellular
ROS/RNS as well. Cellular internalization of GQD was determined using TEM.
Results: GQD prevented SNP-induced apoptosis, caspase activation and mitochondrial depolarization
in neuroblastoma cells. Although GQD diminished the NO levelsin SNP-treated cells, NO scavengers displayed only a slight protection. GQD significantly protected SH-SY5Y cells from neurotoxicity of lightexhausted SNP, incapable of producing NO, implying that protective mechanism is independent of
NO-scavenging. GQD reduced SNP-triggered increase in intracellular levels of ROS, particularly •OH, O2•−
in cells and cell-free condition. Nonselective antioxidants, •OH scavengers and iron chelators, mimicked
GQD cytoprotection, indicating that GQD protect cells by neutralizing •OH generated in the Fenton reaction. Cellular GQD internalization wasrequired for optimal protection since the removal of extracellular GQD by extensive washing partly diminished their protective effect, suggesting that GQD exerted
neuroprotective effect intra- and extracellularly.
Conclusion: By demonstrating that GQD protect neuroblastoma cells from SNP-induced apoptosis by
•OH/NO scavenging, our results suggest that GQD could be valuable candidates for treatment of neurodegenerative diseases associated with oxidative/nitrosative stress.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death
SP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6284
ER  - 

@conference{
author = "Ristić, Biljana and Krunić, Matija and Paunović, Verica and Bošnjak, Mihajlo and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: We examined the molecular mechanisms of graphene quantum dot (GQD)- mediated
protection of SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
Methods: GQD was produced by electrochemical oxidation of graphite and characterized by AFM, UVVIS and FTIR spectroscopy. The antioxidant activity of GQD in cell-free conditions was assessed by DPPH,
NBT and EPR analysis. The neuroprotective potential of GQD was determined by cell viability assays MTT,
CV. Flow cytometry was used to assess markers of apoptosis and GQD scavenging of intracellular
ROS/RNS as well. Cellular internalization of GQD was determined using TEM.
Results: GQD prevented SNP-induced apoptosis, caspase activation and mitochondrial depolarization
in neuroblastoma cells. Although GQD diminished the NO levelsin SNP-treated cells, NO scavengers displayed only a slight protection. GQD significantly protected SH-SY5Y cells from neurotoxicity of lightexhausted SNP, incapable of producing NO, implying that protective mechanism is independent of
NO-scavenging. GQD reduced SNP-triggered increase in intracellular levels of ROS, particularly •OH, O2•−
in cells and cell-free condition. Nonselective antioxidants, •OH scavengers and iron chelators, mimicked
GQD cytoprotection, indicating that GQD protect cells by neutralizing •OH generated in the Fenton reaction. Cellular GQD internalization wasrequired for optimal protection since the removal of extracellular GQD by extensive washing partly diminished their protective effect, suggesting that GQD exerted
neuroprotective effect intra- and extracellularly.
Conclusion: By demonstrating that GQD protect neuroblastoma cells from SNP-induced apoptosis by
•OH/NO scavenging, our results suggest that GQD could be valuable candidates for treatment of neurodegenerative diseases associated with oxidative/nitrosative stress.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death",
pages = "27",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6284"
}

Ristić, B., Krunić, M., Paunović, V., Bošnjak, M., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2023). Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 27.
https://hdl.handle.net/21.15107/rcub_ibiss_6284

Ristić B, Krunić M, Paunović V, Bošnjak M, Tovilović-Kovačević G, Zogović N, Mirčić A, Vuković I, Harhaji-Trajković L, Trajković V. Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:27.
https://hdl.handle.net/21.15107/rcub_ibiss_6284 .

Ristić, Biljana, Krunić, Matija, Paunović, Verica, Bošnjak, Mihajlo, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphen quantum dots protect SH-SY5Y neuronal cells from SNP-indced apoptotic death" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):27,
https://hdl.handle.net/21.15107/rcub_ibiss_6284 .

TY  - JOUR
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6302
AB  - Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.
PB  - Basel: MDPI
T2  - Biomedicines
T1  - Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells
IS  - 10
VL  - 11
DO  - 10.3390/biomedicines11102652
SP  - 2652
ER  - 

@article{
author = "Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2023",
abstract = "Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells",
number = "10",
volume = "11",
doi = "10.3390/biomedicines11102652",
pages = "2652"
}

Despotović, A., Janjetović, K., Zogović, N.,& Tovilović-Kovačević, G.. (2023). Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines
Basel: MDPI., 11(10), 2652.
https://doi.org/10.3390/biomedicines11102652

Despotović A, Janjetović K, Zogović N, Tovilović-Kovačević G. Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines. 2023;11(10):2652.
doi:10.3390/biomedicines11102652 .

Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells" in Biomedicines, 11, no. 10 (2023):2652,
https://doi.org/10.3390/biomedicines11102652 . .

TY  - JOUR
AU  - Ignjatović, Đurđica
AU  - Tovilović-Kovačević, Gordana
AU  - Mićić, Bojana
AU  - Tomić, Mirko
AU  - Đorđević, Ana
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5821
AB  - Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increasein phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.
PB  - Amsterdam: Elsevier
T2  - Hormones and Behavior
T1  - Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome
VL  - 153
DO  - 10.1016/j.yhbeh.2023.105392
SP  - 105392
ER  - 

@article{
author = "Ignjatović, Đurđica and Tovilović-Kovačević, Gordana and Mićić, Bojana and Tomić, Mirko and Đorđević, Ana and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increasein phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.",
publisher = "Amsterdam: Elsevier",
journal = "Hormones and Behavior",
title = "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome",
volume = "153",
doi = "10.1016/j.yhbeh.2023.105392",
pages = "105392"
}

Ignjatović, Đ., Tovilović-Kovačević, G., Mićić, B., Tomić, M., Đorđević, A., Macut, Đ.,& Vojnović-Milutinović, D.. (2023). Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior
Amsterdam: Elsevier., 153, 105392.
https://doi.org/10.1016/j.yhbeh.2023.105392

Ignjatović Đ, Tovilović-Kovačević G, Mićić B, Tomić M, Đorđević A, Macut Đ, Vojnović-Milutinović D. Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior. 2023;153:105392.
doi:10.1016/j.yhbeh.2023.105392 .

Ignjatović, Đurđica, Tovilović-Kovačević, Gordana, Mićić, Bojana, Tomić, Mirko, Đorđević, Ana, Macut, Đuro, Vojnović-Milutinović, Danijela, "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome" in Hormones and Behavior, 153 (2023):105392,
https://doi.org/10.1016/j.yhbeh.2023.105392 . .

TY  - JOUR
AU  - Ignjatović, Đurđica
AU  - Tovilović-Kovačević, Gordana
AU  - Mićić, Bojana
AU  - Tomić, Mirko
AU  - Đorđević, Ana
AU  - Macut, Đuro
AU  - Vojnović-Milutinović, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5820
AB  - Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increase
in phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.
PB  - Amsterdam: Elsevier
T2  - Hormones and Behavior
T1  - Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome
VL  - 153
DO  - 10.1016/j.yhbeh.2023.105392
SP  - 105392
ER  - 

@article{
author = "Ignjatović, Đurđica and Tovilović-Kovačević, Gordana and Mićić, Bojana and Tomić, Mirko and Đorđević, Ana and Macut, Đuro and Vojnović-Milutinović, Danijela",
year = "2023",
abstract = "Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine and metabolic abnormalities such as obesity and insulin resistance. PCOS is also associated with psychiatric disorders and cognitive impairment. The animal model of PCOS was induced by treating rats with 5α dihydrotestosterone (5α-DHT) and additionally modified to induce adiposity by litter size reduction (LSR). Spatial learning and memory were assessed using the Barnes Maze test, and striatal markers of synaptic plasticity were analyzed. Striatal insulin signaling was estimated by the levels of insulin receptor substrate 1 (IRS1), its inhibitory phosphorylation at Ser307, and glycogen synthase kinase-3α/β (GSK3α/β) activity. Both LSR and DHT treatment significantly decreased striatal protein levels of IRS1, followed by increased GSK3α/β activity in small litters. Results of the behavioral study showed that LSR had a negative effect on learning rate and memory retention, whereas DHT treatment did not induce impairment in memory formation. While protein levels of synaptophysin, GAP43, and postsynaptic density protein 95 (PSD-95) were not altered by the treatments, DHT treatment induced an increase
in phosphorylation of PSD-95 at Ser295 in both normal and small litters. This study revealed that LSR and DHT treatment suppressed insulin signaling by downregulating IRS1 in the striatum. However, DHT treatment did not have an adverse effect on learning and memory, probably due to compensatory elevation in pPSD-95-Ser295, which had a positive effect on synaptic strength. This implies that hyperandrogenemia in this setting does not represent a threat to spatial learning and memory, opposite to the effect of overnutrition-related adiposity.",
publisher = "Amsterdam: Elsevier",
journal = "Hormones and Behavior",
title = "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome",
volume = "153",
doi = "10.1016/j.yhbeh.2023.105392",
pages = "105392"
}

Ignjatović, Đ., Tovilović-Kovačević, G., Mićić, B., Tomić, M., Đorđević, A., Macut, Đ.,& Vojnović-Milutinović, D.. (2023). Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior
Amsterdam: Elsevier., 153, 105392.
https://doi.org/10.1016/j.yhbeh.2023.105392

Ignjatović Đ, Tovilović-Kovačević G, Mićić B, Tomić M, Đorđević A, Macut Đ, Vojnović-Milutinović D. Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome. in Hormones and Behavior. 2023;153:105392.
doi:10.1016/j.yhbeh.2023.105392 .

Ignjatović, Đurđica, Tovilović-Kovačević, Gordana, Mićić, Bojana, Tomić, Mirko, Đorđević, Ana, Macut, Đuro, Vojnović-Milutinović, Danijela, "Effects of early life overnutrition and hyperandrogenism on spatial learning and memory in a rat model of polycystic ovary syndrome" in Hormones and Behavior, 153 (2023):105392,
https://doi.org/10.1016/j.yhbeh.2023.105392 . .

TY  - CONF
AU  - Pergal, Marija V.
AU  - Brkljačić, Jelena
AU  - Vasiljević Radović, Dana
AU  - Pergal, Miodrag M.
AU  - Pešić, Ivan
AU  - Dević, Gordana
AU  - Tovilović-Kovačević, Gordana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6192
AB  - Polyurethane (PU) nanocomposite materials, offer very desirable advantages over pure PU materials,as the nanocomposites have enhanced thermal, surface, mechanical and biological properties. The main goal of this study was to develop a new kind of novel nanocomposites consisting of crosslinked PUs (based on poly(dimetylsiloxane) and hyperbranched polyester) and ferrite nanoparticles (based on copper and zinc) for possible application as coatings on biomedical devices and implants. A series of PU/ferrite nanocomposites was prepared by in situ polymerization in solution. Characterization of prepared nanocomposites nanocomposites was conducted by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Copper and zinc releases were investigated by microwave plasma atomic emission spectrometry (MP-AES). Characteristics of the prepared nanocomposites when in contact with a biological environment were examined through testing their biocompatibility, and adhesion of fibroblast cells. The presence of the nanoferrite nanoparticles influenced on surface and biological properties of PU nanocomposites. The prepared PU nanocomposites with noncytotoxic chemistry could be used as promising materials for vascular implants development.
PB  - Belgrade: Serbian Ceramic Society
C3  - Program and the Book of Abstracts: Serbian Ceramic Society Conference Advanced Ceramics and Application 11: New Frontiers in Multifunctional Material Science and Processing; 2023 Sep 18-20; Belgrade, Serbia
T1  - Characterization of polyurethane/ferrite nanocomposites
SP  - 65
EP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6192
ER  - 

@conference{
author = "Pergal, Marija V. and Brkljačić, Jelena and Vasiljević Radović, Dana and Pergal, Miodrag M. and Pešić, Ivan and Dević, Gordana and Tovilović-Kovačević, Gordana",
year = "2023",
abstract = "Polyurethane (PU) nanocomposite materials, offer very desirable advantages over pure PU materials,as the nanocomposites have enhanced thermal, surface, mechanical and biological properties. The main goal of this study was to develop a new kind of novel nanocomposites consisting of crosslinked PUs (based on poly(dimetylsiloxane) and hyperbranched polyester) and ferrite nanoparticles (based on copper and zinc) for possible application as coatings on biomedical devices and implants. A series of PU/ferrite nanocomposites was prepared by in situ polymerization in solution. Characterization of prepared nanocomposites nanocomposites was conducted by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Copper and zinc releases were investigated by microwave plasma atomic emission spectrometry (MP-AES). Characteristics of the prepared nanocomposites when in contact with a biological environment were examined through testing their biocompatibility, and adhesion of fibroblast cells. The presence of the nanoferrite nanoparticles influenced on surface and biological properties of PU nanocomposites. The prepared PU nanocomposites with noncytotoxic chemistry could be used as promising materials for vascular implants development.",
publisher = "Belgrade: Serbian Ceramic Society",
journal = "Program and the Book of Abstracts: Serbian Ceramic Society Conference Advanced Ceramics and Application 11: New Frontiers in Multifunctional Material Science and Processing; 2023 Sep 18-20; Belgrade, Serbia",
title = "Characterization of polyurethane/ferrite nanocomposites",
pages = "65-65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6192"
}

Pergal, M. V., Brkljačić, J., Vasiljević Radović, D., Pergal, M. M., Pešić, I., Dević, G.,& Tovilović-Kovačević, G.. (2023). Characterization of polyurethane/ferrite nanocomposites. in Program and the Book of Abstracts: Serbian Ceramic Society Conference Advanced Ceramics and Application 11: New Frontiers in Multifunctional Material Science and Processing; 2023 Sep 18-20; Belgrade, Serbia
Belgrade: Serbian Ceramic Society., 65-65.
https://hdl.handle.net/21.15107/rcub_ibiss_6192

Pergal MV, Brkljačić J, Vasiljević Radović D, Pergal MM, Pešić I, Dević G, Tovilović-Kovačević G. Characterization of polyurethane/ferrite nanocomposites. in Program and the Book of Abstracts: Serbian Ceramic Society Conference Advanced Ceramics and Application 11: New Frontiers in Multifunctional Material Science and Processing; 2023 Sep 18-20; Belgrade, Serbia. 2023;:65-65.
https://hdl.handle.net/21.15107/rcub_ibiss_6192 .

Pergal, Marija V., Brkljačić, Jelena, Vasiljević Radović, Dana, Pergal, Miodrag M., Pešić, Ivan, Dević, Gordana, Tovilović-Kovačević, Gordana, "Characterization of polyurethane/ferrite nanocomposites" in Program and the Book of Abstracts: Serbian Ceramic Society Conference Advanced Ceramics and Application 11: New Frontiers in Multifunctional Material Science and Processing; 2023 Sep 18-20; Belgrade, Serbia (2023):65-65,
https://hdl.handle.net/21.15107/rcub_ibiss_6192 .

TY  - CONF
AU  - Pergal, Marija
AU  - Brkljačić, Jelena
AU  - Pešić, Ivan
AU  - Dević, Gordana
AU  - Dojčinović, Biljana P.
AU  - Antić, Bratislav
AU  - Tovilović-Kovačević, Gordana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6191
AB  - Polyurethane (PU) and PU nanocomposites with good biocompatibility and mechanical properties can be used as the biomedical matrix and tissue engineering biomaterials. Magnetic nanoparticles, especially ferrite nanoparticles have attracted much interest due to their specific physicochemical properties in various areas including magnetic recording, biosensing, catalyst, drug delivery systems, magnetic resonance imaging (MRI) and cancer therapy. Despite all these advantages, the nanoparticle agglomeration reduces the efficiency of the nanoparticles, so the nanoparticle incorporation into an appropriate polymeric matrix to prepare organic-inorganic nanocomposites is a right direction in the current scenario of biomedical nanotechnology. In this study, organic-inorganic PU nanocomposites based on zinc and copper ferrites and with the same composition of PU were prepared. The properties of PU nanocomposites were evaluated by nanoindentation, water contact angle and water absorption measurements. The presence of the nanoferrite nanoparticles affects properties of PU nanocomposites such as bulk morphology, mechanical, and biological properties. The biocompatibility of PU nanocomposites was investigated by MTT assay and cell attachment using endothelial cells. According to the results, the prepared PU nanocomposites with noncytotoxic chemistry could be a potential choice for vascular implants development.
PB  - Niš, Serbia: RAD Centre
C3  - Book of Abstracts: Eleventh International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2023; 2023 Jun 19-23; Herceg Novi, Montenegro
T1  - Organic-inorganic nanocomposites for biomedical applications
DO  - 10.21175/rad.abstr.book.2023.19.20
SP  - 99
EP  - 99
ER  - 

@conference{
author = "Pergal, Marija and Brkljačić, Jelena and Pešić, Ivan and Dević, Gordana and Dojčinović, Biljana P. and Antić, Bratislav and Tovilović-Kovačević, Gordana",
year = "2023",
abstract = "Polyurethane (PU) and PU nanocomposites with good biocompatibility and mechanical properties can be used as the biomedical matrix and tissue engineering biomaterials. Magnetic nanoparticles, especially ferrite nanoparticles have attracted much interest due to their specific physicochemical properties in various areas including magnetic recording, biosensing, catalyst, drug delivery systems, magnetic resonance imaging (MRI) and cancer therapy. Despite all these advantages, the nanoparticle agglomeration reduces the efficiency of the nanoparticles, so the nanoparticle incorporation into an appropriate polymeric matrix to prepare organic-inorganic nanocomposites is a right direction in the current scenario of biomedical nanotechnology. In this study, organic-inorganic PU nanocomposites based on zinc and copper ferrites and with the same composition of PU were prepared. The properties of PU nanocomposites were evaluated by nanoindentation, water contact angle and water absorption measurements. The presence of the nanoferrite nanoparticles affects properties of PU nanocomposites such as bulk morphology, mechanical, and biological properties. The biocompatibility of PU nanocomposites was investigated by MTT assay and cell attachment using endothelial cells. According to the results, the prepared PU nanocomposites with noncytotoxic chemistry could be a potential choice for vascular implants development.",
publisher = "Niš, Serbia: RAD Centre",
journal = "Book of Abstracts: Eleventh International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2023; 2023 Jun 19-23; Herceg Novi, Montenegro",
title = "Organic-inorganic nanocomposites for biomedical applications",
doi = "10.21175/rad.abstr.book.2023.19.20",
pages = "99-99"
}

Pergal, M., Brkljačić, J., Pešić, I., Dević, G., Dojčinović, B. P., Antić, B.,& Tovilović-Kovačević, G.. (2023). Organic-inorganic nanocomposites for biomedical applications. in Book of Abstracts: Eleventh International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2023; 2023 Jun 19-23; Herceg Novi, Montenegro
Niš, Serbia: RAD Centre., 99-99.
https://doi.org/10.21175/rad.abstr.book.2023.19.20

Pergal M, Brkljačić J, Pešić I, Dević G, Dojčinović BP, Antić B, Tovilović-Kovačević G. Organic-inorganic nanocomposites for biomedical applications. in Book of Abstracts: Eleventh International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2023; 2023 Jun 19-23; Herceg Novi, Montenegro. 2023;:99-99.
doi:10.21175/rad.abstr.book.2023.19.20 .

Pergal, Marija, Brkljačić, Jelena, Pešić, Ivan, Dević, Gordana, Dojčinović, Biljana P., Antić, Bratislav, Tovilović-Kovačević, Gordana, "Organic-inorganic nanocomposites for biomedical applications" in Book of Abstracts: Eleventh International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2023; 2023 Jun 19-23; Herceg Novi, Montenegro (2023):99-99,
https://doi.org/10.21175/rad.abstr.book.2023.19.20 . .

TY  - CONF
AU  - Zeković, Janko
AU  - Vidičević Novaković, Sašenka
AU  - Tasić, Jelena
AU  - Stanojević, Željka
AU  - Milovanović, Andona
AU  - Tomonjić, Nina
AU  - Petričević, Saša
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Trajković, Vladimir
AU  - Isaković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5839
AB  - Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5839
ER  - 

@conference{
author = "Zeković, Janko and Vidičević Novaković, Sašenka and Tasić, Jelena and Stanojević, Željka and Milovanović, Andona and Tomonjić, Nina and Petričević, Saša and Zogović, Nevena and Tovilović-Kovačević, Gordana and Trajković, Vladimir and Isaković, Aleksandra",
year = "2023",
abstract = "Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5839"
}

Zeković, J., Vidičević Novaković, S., Tasić, J., Stanojević, Ž., Milovanović, A., Tomonjić, N., Petričević, S., Zogović, N., Tovilović-Kovačević, G., Trajković, V.,& Isaković, A.. (2023). Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839

Zeković J, Vidičević Novaković S, Tasić J, Stanojević Ž, Milovanović A, Tomonjić N, Petričević S, Zogović N, Tovilović-Kovačević G, Trajković V, Isaković A. Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

Zeković, Janko, Vidičević Novaković, Sašenka, Tasić, Jelena, Stanojević, Željka, Milovanović, Andona, Tomonjić, Nina, Petričević, Saša, Zogović, Nevena, Tovilović-Kovačević, Gordana, Trajković, Vladimir, Isaković, Aleksandra, "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):80,
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

TY  - CONF
AU  - Tovilović-Kovačević, Gordana
AU  - Krstić-Milošević, Dijana
AU  - Vinterhalter, Branka
AU  - Toljić, Mina
AU  - Perović, Vladimir
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Zogović, Nevena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5317
AB  - Глиобластом je најчешћи и најагресивнији тип тумора централног нервног система код одраслих. Циљ ове студије је био да се процени антиглиомски потенцијал екстраката коренова Gentiana dinarica у култури U251 ћелија хуманог глиобластома. Метанолни екстракти су добијени из нетрансформисаних коренова G. dinarica (екстракт 1, Е1) и трансгених коренова добијених коришћењем два соја Agrobacterium rhizogenes: A4M70GUS (екстракт 2, Е2) и 15834/PI (екстракт 3, Е3). Трансформацијом коренова са A. rhizogenes стимулисана је продукција ксантона, секундарних метаболита са доказаним антиканцерским ефектом. За разлику од Е1 и Е2, Е3 је снажно инхибирао раст U251 ћелија, изазвао застој ћелијског циклуса у G2/M фази и повећао експресију маркера диференцијације – астроцитног глијалног фибриларног киселог протеина (GFAP) и неуронског β-тубулина. Е3 је стимулисао Akt/mTOR-зависну аутофагију, на шта је указивало повећање нивоа аутофагног маркера LC3-II протеина и појачана деградација селективне аутофагне мете протеина p62. Инхибиција аутофагије је спречила експресију маркера диференцијације, без утицаја на застој у ћелијском циклусу. Е3 је повећао и нивое оксидативног стреса у ћелији, а антиоксиданси N-ацетил цистеин (NAC) и витамин Е су инхибирали и аутофагију и диференцијацију U251 ћелија изазвану Е3. Активна компонента Е3 је највероватније ксантонски агликон норсверцијанин, најзаступљеније једињење у Е3. Норсверцијанин је, као и Е3, зауставио пролиферацију U251 ћелија у G2/M фази ћелијског циклуса и изазвао диференцијацију, аутофагију и оксидативни стрес. Резултати ове студије указују да би Е3 и норсверцијанин могли бити кандидати за диференцијациону терапију глиобластома.
AB  - Glioblastom je najčešći i najagresivniji tip tumora centralnog nervnog sistema kod odraslih. Cilj ove studije je bio da se proceni antigliomski potencijal ekstrakata korenova Gentiana dinarica u kulturi U251 ćelija humanog glioblastoma. Metanolni ekstrakti su dobijeni iz netransformisanih korenova G. dinarica (ekstrakt 1, E1) i transgenih korenova dobijenih korišćenjem dva soja Agrobacterium rhizogenes: A4M70GUS (ekstrakt 2, E2) i 15834/PI (ekstrakt 3, E3). Transformacijom korenova sa A. rhizogenes stimulisana je produkcija ksantona, sekundarnih metabolita sa dokazanim antikancerskim efektom. Za razliku od E1 i E2, E3 je snažno inhibirao rast U251 ćelija, izazvao zastoj ćelijskog ciklusa u G2/M fazi i povećao ekspresiju markera diferencijacije – astrocitnog glijalnog fibrilarnog kiselog proteina (GFAP) i neuronskog β-tubulina. E3 je stimulisao Akt/mTOR-zavisnu autofagiju, na šta je ukazivalo povećanje nivoa autofagnog markera LC3-II proteina i pojačana degradacija selektivne autofagne mete proteina p62. Inhibicija autofagije je sprečila ekspresiju markera diferencijacije, bez uticaja na zastoj u ćelijskom ciklusu. E3 je povećao i nivoe oksidativnog stresa u ćeliji, a antioksidansi N-acetil cistein (NAC) i vitamin E su inhibirali i autofagiju i diferencijaciju U251 ćelija izazvanu E3. Aktivna komponenta E3 je najverovatnije ksantonski aglikon norsvercijanin, najzastupljenije jedinjenje u E3. Norsvercijanin je, kao i E3, zaustavio proliferaciju U251 ćelija u G2/M fazi ćelijskog ciklusa i izazvao diferencijaciju, autofagiju i oksidativni stres. Rezultati ove studije ukazuju da bi E3 i norsvercijanin mogli biti kandidati za diferencijacionu terapiju glioblastoma.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima
T1  - Антиглиомски ефекат екстракта корена Gentiana dinarica Beck. обогаћеног ксантонима
SP  - 280
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5317
ER  - 

@conference{
author = "Tovilović-Kovačević, Gordana and Krstić-Milošević, Dijana and Vinterhalter, Branka and Toljić, Mina and Perović, Vladimir and Trajković, Vladimir and Harhaji-Trajković, Ljubica and Zogović, Nevena",
year = "2022",
abstract = "Глиобластом je најчешћи и најагресивнији тип тумора централног нервног система код одраслих. Циљ ове студије је био да се процени антиглиомски потенцијал екстраката коренова Gentiana dinarica у култури U251 ћелија хуманог глиобластома. Метанолни екстракти су добијени из нетрансформисаних коренова G. dinarica (екстракт 1, Е1) и трансгених коренова добијених коришћењем два соја Agrobacterium rhizogenes: A4M70GUS (екстракт 2, Е2) и 15834/PI (екстракт 3, Е3). Трансформацијом коренова са A. rhizogenes стимулисана је продукција ксантона, секундарних метаболита са доказаним антиканцерским ефектом. За разлику од Е1 и Е2, Е3 је снажно инхибирао раст U251 ћелија, изазвао застој ћелијског циклуса у G2/M фази и повећао експресију маркера диференцијације – астроцитног глијалног фибриларног киселог протеина (GFAP) и неуронског β-тубулина. Е3 је стимулисао Akt/mTOR-зависну аутофагију, на шта је указивало повећање нивоа аутофагног маркера LC3-II протеина и појачана деградација селективне аутофагне мете протеина p62. Инхибиција аутофагије је спречила експресију маркера диференцијације, без утицаја на застој у ћелијском циклусу. Е3 је повећао и нивое оксидативног стреса у ћелији, а антиоксиданси N-ацетил цистеин (NAC) и витамин Е су инхибирали и аутофагију и диференцијацију U251 ћелија изазвану Е3. Активна компонента Е3 је највероватније ксантонски агликон норсверцијанин, најзаступљеније једињење у Е3. Норсверцијанин је, као и Е3, зауставио пролиферацију U251 ћелија у G2/M фази ћелијског циклуса и изазвао диференцијацију, аутофагију и оксидативни стрес. Резултати ове студије указују да би Е3 и норсверцијанин могли бити кандидати за диференцијациону терапију глиобластома., Glioblastom je najčešći i najagresivniji tip tumora centralnog nervnog sistema kod odraslih. Cilj ove studije je bio da se proceni antigliomski potencijal ekstrakata korenova Gentiana dinarica u kulturi U251 ćelija humanog glioblastoma. Metanolni ekstrakti su dobijeni iz netransformisanih korenova G. dinarica (ekstrakt 1, E1) i transgenih korenova dobijenih korišćenjem dva soja Agrobacterium rhizogenes: A4M70GUS (ekstrakt 2, E2) i 15834/PI (ekstrakt 3, E3). Transformacijom korenova sa A. rhizogenes stimulisana je produkcija ksantona, sekundarnih metabolita sa dokazanim antikancerskim efektom. Za razliku od E1 i E2, E3 je snažno inhibirao rast U251 ćelija, izazvao zastoj ćelijskog ciklusa u G2/M fazi i povećao ekspresiju markera diferencijacije – astrocitnog glijalnog fibrilarnog kiselog proteina (GFAP) i neuronskog β-tubulina. E3 je stimulisao Akt/mTOR-zavisnu autofagiju, na šta je ukazivalo povećanje nivoa autofagnog markera LC3-II proteina i pojačana degradacija selektivne autofagne mete proteina p62. Inhibicija autofagije je sprečila ekspresiju markera diferencijacije, bez uticaja na zastoj u ćelijskom ciklusu. E3 je povećao i nivoe oksidativnog stresa u ćeliji, a antioksidansi N-acetil cistein (NAC) i vitamin E su inhibirali i autofagiju i diferencijaciju U251 ćelija izazvanu E3. Aktivna komponenta E3 je najverovatnije ksantonski aglikon norsvercijanin, najzastupljenije jedinjenje u E3. Norsvercijanin je, kao i E3, zaustavio proliferaciju U251 ćelija u G2/M fazi ćelijskog ciklusa i izazvao diferencijaciju, autofagiju i oksidativni stres. Rezultati ove studije ukazuju da bi E3 i norsvercijanin mogli biti kandidati za diferencijacionu terapiju glioblastoma.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima, Антиглиомски ефекат екстракта корена Gentiana dinarica Beck. обогаћеног ксантонима",
pages = "280",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5317"
}

Tovilović-Kovačević, G., Krstić-Milošević, D., Vinterhalter, B., Toljić, M., Perović, V., Trajković, V., Harhaji-Trajković, L.,& Zogović, N.. (2022). Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 280.
https://hdl.handle.net/21.15107/rcub_ibiss_5317

Tovilović-Kovačević G, Krstić-Milošević D, Vinterhalter B, Toljić M, Perović V, Trajković V, Harhaji-Trajković L, Zogović N. Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:280.
https://hdl.handle.net/21.15107/rcub_ibiss_5317 .

Tovilović-Kovačević, Gordana, Krstić-Milošević, Dijana, Vinterhalter, Branka, Toljić, Mina, Perović, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, Zogović, Nevena, "Antigliomski efekat ekstrakta korena Gentiana dinarica Beck. obogaćenog ksantonima" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):280,
https://hdl.handle.net/21.15107/rcub_ibiss_5317 .

TY  - JOUR
AU  - Despotović, Ana
AU  - Mirčić, Aleksandar
AU  - Misirlić-Denčić, Sonja
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2022
UR  - https://www.hindawi.com/journals/omcl/2022/2998132/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5078
AB  - We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.
PB  - London: Hindawi Ltd.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells
VL  - 2022
DO  - 10.1155/2022/2998132
SP  - 2998132
ER  - 

@article{
author = "Despotović, Ana and Mirčić, Aleksandar and Misirlić-Denčić, Sonja and Harhaji-Trajković, Ljubica and Trajković, Vladimir and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2022",
abstract = "We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.",
publisher = "London: Hindawi Ltd.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells",
volume = "2022",
doi = "10.1155/2022/2998132",
pages = "2998132"
}

Despotović, A., Mirčić, A., Misirlić-Denčić, S., Harhaji-Trajković, L., Trajković, V., Zogović, N.,& Tovilović-Kovačević, G.. (2022). Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. in Oxidative Medicine and Cellular Longevity
London: Hindawi Ltd.., 2022, 2998132.
https://doi.org/10.1155/2022/2998132

Despotović A, Mirčić A, Misirlić-Denčić S, Harhaji-Trajković L, Trajković V, Zogović N, Tovilović-Kovačević G. Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. in Oxidative Medicine and Cellular Longevity. 2022;2022:2998132.
doi:10.1155/2022/2998132 .

Despotović, Ana, Mirčić, Aleksandar, Misirlić-Denčić, Sonja, Harhaji-Trajković, Ljubica, Trajković, Vladimir, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells" in Oxidative Medicine and Cellular Longevity, 2022 (2022):2998132,
https://doi.org/10.1155/2022/2998132 . .

TY  - CONF
AU  - Janjetović, Kristina
AU  - Stamenković, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Despotović, Ana
AU  - Stevanović, Danijela
AU  - Mandić, Miloš
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5737
AB  - I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola.
AB  - И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antikancerski potencijal inhibitora protonske pumpe pantoprazola
T1  - Антиканцерски потенцијал инхибитора протонске пумпе пантопразола
SP  - 285
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5737
ER  - 

@conference{
author = "Janjetović, Kristina and Stamenković, Marina and Tovilović-Kovačević, Gordana and Zogović, Nevena and Despotović, Ana and Stevanović, Danijela and Mandić, Miloš and Kosić, Milica and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Trajković, Vladimir",
year = "2022",
abstract = "I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola., И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antikancerski potencijal inhibitora protonske pumpe pantoprazola, Антиканцерски потенцијал инхибитора протонске пумпе пантопразола",
pages = "285",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5737"
}

Janjetović, K., Stamenković, M., Tovilović-Kovačević, G., Zogović, N., Despotović, A., Stevanović, D., Mandić, M., Kosić, M., Paunović, V., Vučićević, L., Misirkić Marjanović, M.,& Trajković, V.. (2022). Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737

Janjetović K, Stamenković M, Tovilović-Kovačević G, Zogović N, Despotović A, Stevanović D, Mandić M, Kosić M, Paunović V, Vučićević L, Misirkić Marjanović M, Trajković V. Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

Janjetović, Kristina, Stamenković, Marina, Tovilović-Kovačević, Gordana, Zogović, Nevena, Despotović, Ana, Stevanović, Danijela, Mandić, Miloš, Kosić, Milica, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Trajković, Vladimir, "Antikancerski potencijal inhibitora protonske pumpe pantoprazola" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):285,
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

TY  - CONF
AU  - Jeremić, Marija
AU  - Jovanović, Maja
AU  - Tovilović-Kovačević, Gordana
AU  - Harhaji-Trajković, Ljubica
AU  - Zogović, Nevena
AU  - Vukojević, Milica
AU  - Kostić, Vladimir
AU  - Marković, Ivanka D.
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4450
AB  - Alpha-synuclein (ASYN) is regarded as one of the key culprits in
pathogenesis of synucleinopathies, including Parkinson’s disease,
and impaired regulation of autophagy is associated with the
ASYN aggregation. Autophagy is regulated by complex mechanisms,
including AMP activated protein kinase (AMPK), a key
energy sensor regulating cellular metabolism to maintain energy
homeostasis. The aim of our study was to investigate the role of
AMPK and autophagy in neurotoxic effect of secreted ASYN, as
well as dopamine-modified and nitrated recombinant wild-type
ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y
cells. The culture supernatant from neuroblastoma cells stably
expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed
by immunoblot, following lyophilisation. The CM, as well as
recombinant dopamine-modified or nitrated ASYN, all reduced
viability in differentiated SH-SY5Y cells. This decrease in viability
was accompanied by reduced AMPK activation, increased
conversion of LC3-I to LC3-II and increase in Beclin-1 level, as
demonstrated by immunoblot. Pharmacological activators of
AMPK and autophagy (metformin and AICAR) significantly
increased the cells’ viability in the presence of CM and modified
ASYN forms. Level of AMPK-activated pULK was reduced in
presence of CM, but pharmacological activators of AMPK
reversed that effect. Pharmacological inhibitors of autophagy,
further reduced cell viability in the presence of extracellular
ASYN. The shRNA-mediated LC3 downregulation, as well as
the RNA interference-mediated knockdown of ATG7 gene, both
important for autophagosome biogenesis/maturation, increased
sensitivity of SH-SY5Y cells to the extracellular ASYN-induced
toxicity. These data demonstrate the protective role of AMPK
and autophagy against the toxicity of extracellular ASYN, suggesting
that their modulation may be a promising neuroprotective
strategy in Parkinson’s disease.
PB  - Hoboken: Wiley
C3  - FEBS OpenBio
T1  - Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy
IS  - Supplement 1
VL  - 11
SP  - 463
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4450
ER  - 

@conference{
author = "Jeremić, Marija and Jovanović, Maja and Tovilović-Kovačević, Gordana and Harhaji-Trajković, Ljubica and Zogović, Nevena and Vukojević, Milica and Kostić, Vladimir and Marković, Ivanka D. and Trajković, Vladimir",
year = "2021",
abstract = "Alpha-synuclein (ASYN) is regarded as one of the key culprits in
pathogenesis of synucleinopathies, including Parkinson’s disease,
and impaired regulation of autophagy is associated with the
ASYN aggregation. Autophagy is regulated by complex mechanisms,
including AMP activated protein kinase (AMPK), a key
energy sensor regulating cellular metabolism to maintain energy
homeostasis. The aim of our study was to investigate the role of
AMPK and autophagy in neurotoxic effect of secreted ASYN, as
well as dopamine-modified and nitrated recombinant wild-type
ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y
cells. The culture supernatant from neuroblastoma cells stably
expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed
by immunoblot, following lyophilisation. The CM, as well as
recombinant dopamine-modified or nitrated ASYN, all reduced
viability in differentiated SH-SY5Y cells. This decrease in viability
was accompanied by reduced AMPK activation, increased
conversion of LC3-I to LC3-II and increase in Beclin-1 level, as
demonstrated by immunoblot. Pharmacological activators of
AMPK and autophagy (metformin and AICAR) significantly
increased the cells’ viability in the presence of CM and modified
ASYN forms. Level of AMPK-activated pULK was reduced in
presence of CM, but pharmacological activators of AMPK
reversed that effect. Pharmacological inhibitors of autophagy,
further reduced cell viability in the presence of extracellular
ASYN. The shRNA-mediated LC3 downregulation, as well as
the RNA interference-mediated knockdown of ATG7 gene, both
important for autophagosome biogenesis/maturation, increased
sensitivity of SH-SY5Y cells to the extracellular ASYN-induced
toxicity. These data demonstrate the protective role of AMPK
and autophagy against the toxicity of extracellular ASYN, suggesting
that their modulation may be a promising neuroprotective
strategy in Parkinson’s disease.",
publisher = "Hoboken: Wiley",
journal = "FEBS OpenBio",
title = "Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy",
number = "Supplement 1",
volume = "11",
pages = "463",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4450"
}

Jeremić, M., Jovanović, M., Tovilović-Kovačević, G., Harhaji-Trajković, L., Zogović, N., Vukojević, M., Kostić, V., Marković, I. D.,& Trajković, V.. (2021). Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy. in FEBS OpenBio
Hoboken: Wiley., 11(Supplement 1), 463.
https://hdl.handle.net/21.15107/rcub_ibiss_4450

Jeremić M, Jovanović M, Tovilović-Kovačević G, Harhaji-Trajković L, Zogović N, Vukojević M, Kostić V, Marković ID, Trajković V. Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy. in FEBS OpenBio. 2021;11(Supplement 1):463.
https://hdl.handle.net/21.15107/rcub_ibiss_4450 .

Jeremić, Marija, Jovanović, Maja, Tovilović-Kovačević, Gordana, Harhaji-Trajković, Ljubica, Zogović, Nevena, Vukojević, Milica, Kostić, Vladimir, Marković, Ivanka D., Trajković, Vladimir, "Neurotoxic effect of extracellular alpha-synuclein can be alleviated by AMPK and autophagy" in FEBS OpenBio, 11, no. Supplement 1 (2021):463,
https://hdl.handle.net/21.15107/rcub_ibiss_4450 .

TY  - CONF
AU  - Despotović, Ana
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4724
AB  - The aim of this study was to investigate the role of necroptosis inhibitor necrostatin-1
(Nec-1) in death of human glioblastoma U251 cells exposed to ascorbic acid (AA), menadione(MD),
and their combination, in vitro. Nec-1 augmented cytotoxicity of AA+MD, and slightly increased
death of MD-treated U251 cells, as assessed by crystal violet (CV) assay. In line with previous, flow
cytometric analysis of annexin/propidium iodide-stained cells showed that Nec-1 triggered cell
death in MD and significantly enhanced ability of AA+MD to increase number of necrotic cells,
substantiating necrosis as the mechanism of U251 cell death induced by combined treatments
– AA+MD, Nec-1+MD, and Nec-1+AA+MD. Further, Nec-1 elevated mitochondrial and cellular
reactive oxygen species (ROS) generated by both MD and AA+MD co-treatment, as assessed
by flow cytometry analysis of MitoSOX- and DHR-stained cells, respectively. N-acetyl cysteine
(NAC), a well-known antioxidant, opposed U251 cell death induced by AA+MD, Nec-1+MD, and
Nec-1+AA+MD, indicating crucial role of oxidative stress in Nec-1-potentiated cytotoxicity of
MD and AA+MD. Also, Nec-1 activated AMP-activated protein kinase (AMPK), and its effector
molecule ULK1 (Ser317) over the level induced by MD and AA+MD, as showed by immunoblot.
AMPK, highly conserved serine/threonine protein kinase, is activated under the conditions of
oxidative stress probably as a consequence of depleted cellular ATP and elevated AMP levels.
This result implies important role of AMPK in necrosis detected in AA+MD-, Nec-1+MD-, and
Nec-1+AA+MD-treated U251 cells. Therefore, it can be concluded that ability of Nec-1 to enhance
cytotoxic potential of AA+MD co-treatment and trigger cytotoxicity of MD is associated with its
capacity to amplify cellular and mitochondrial ROS production, leading to necrosis-like cell
death of U251 cells. Obtained results reveal potential use of Nec-1 as anti-glioblastoma agent,
especially in combination with AA+MD.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line
DO  - 10.1016/j.freeradbiomed.2021.08.081
SP  - 78
ER  - 

@conference{
author = "Despotović, Ana and Harhaji-Trajković, Ljubica and Trajković, Vladimir and Tovilović-Kovačević, Gordana and Zogović, Nevena",
year = "2021",
abstract = "The aim of this study was to investigate the role of necroptosis inhibitor necrostatin-1
(Nec-1) in death of human glioblastoma U251 cells exposed to ascorbic acid (AA), menadione(MD),
and their combination, in vitro. Nec-1 augmented cytotoxicity of AA+MD, and slightly increased
death of MD-treated U251 cells, as assessed by crystal violet (CV) assay. In line with previous, flow
cytometric analysis of annexin/propidium iodide-stained cells showed that Nec-1 triggered cell
death in MD and significantly enhanced ability of AA+MD to increase number of necrotic cells,
substantiating necrosis as the mechanism of U251 cell death induced by combined treatments
– AA+MD, Nec-1+MD, and Nec-1+AA+MD. Further, Nec-1 elevated mitochondrial and cellular
reactive oxygen species (ROS) generated by both MD and AA+MD co-treatment, as assessed
by flow cytometry analysis of MitoSOX- and DHR-stained cells, respectively. N-acetyl cysteine
(NAC), a well-known antioxidant, opposed U251 cell death induced by AA+MD, Nec-1+MD, and
Nec-1+AA+MD, indicating crucial role of oxidative stress in Nec-1-potentiated cytotoxicity of
MD and AA+MD. Also, Nec-1 activated AMP-activated protein kinase (AMPK), and its effector
molecule ULK1 (Ser317) over the level induced by MD and AA+MD, as showed by immunoblot.
AMPK, highly conserved serine/threonine protein kinase, is activated under the conditions of
oxidative stress probably as a consequence of depleted cellular ATP and elevated AMP levels.
This result implies important role of AMPK in necrosis detected in AA+MD-, Nec-1+MD-, and
Nec-1+AA+MD-treated U251 cells. Therefore, it can be concluded that ability of Nec-1 to enhance
cytotoxic potential of AA+MD co-treatment and trigger cytotoxicity of MD is associated with its
capacity to amplify cellular and mitochondrial ROS production, leading to necrosis-like cell
death of U251 cells. Obtained results reveal potential use of Nec-1 as anti-glioblastoma agent,
especially in combination with AA+MD.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line",
doi = "10.1016/j.freeradbiomed.2021.08.081",
pages = "78"
}

Despotović, A., Harhaji-Trajković, L., Trajković, V., Tovilović-Kovačević, G.,& Zogović, N.. (2021). Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 78.
https://doi.org/10.1016/j.freeradbiomed.2021.08.081

Despotović A, Harhaji-Trajković L, Trajković V, Tovilović-Kovačević G, Zogović N. Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:78.
doi:10.1016/j.freeradbiomed.2021.08.081 .

Despotović, Ana, Harhaji-Trajković, Ljubica, Trajković, Vladimir, Tovilović-Kovačević, Gordana, Zogović, Nevena, "Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):78,
https://doi.org/10.1016/j.freeradbiomed.2021.08.081 . .

TY  - CONF
AU  - Harhaji-Trajković, Ljubica
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Zogović, Nevena
AU  - Mandić, Miloš
AU  - Tovilović-Kovačević, Gordana
AU  - Janjetović, Kristina
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.sdir.ac.rs/apstrakti-SDIR-5/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4709
AB  - Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency 
substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional 
intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, 
which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting 
of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human 
glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death 
were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by 
appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) 
rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization 
triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived 
cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity 
with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the 
cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 
2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both 
serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was 
irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth 
in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression 
and lysosomal destabilization might be exploited in cancer therapy.
PB  - Beograd : Srpsko društvo istraživača raka
C3  - 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“
T1  - Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy
SP  - 8
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4709
ER  - 

@conference{
author = "Harhaji-Trajković, Ljubica and Kosić, Milica and Paunović, Verica and Ristić, Biljana and Bošnjak, Mihajlo and Zogović, Nevena and Mandić, Miloš and Tovilović-Kovačević, Gordana and Janjetović, Kristina and Trajković, Vladimir",
year = "2021",
abstract = "Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency 
substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional 
intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, 
which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting 
of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human 
glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death 
were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by 
appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) 
rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization 
triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived 
cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity 
with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the 
cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 
2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both 
serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was 
irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth 
in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression 
and lysosomal destabilization might be exploited in cancer therapy.",
publisher = "Beograd : Srpsko društvo istraživača raka",
journal = "5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“",
title = "Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy",
pages = "8",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4709"
}

Harhaji-Trajković, L., Kosić, M., Paunović, V., Ristić, B., Bošnjak, M., Zogović, N., Mandić, M., Tovilović-Kovačević, G., Janjetović, K.,& Trajković, V.. (2021). Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy. in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“
Beograd : Srpsko društvo istraživača raka., 8.
https://hdl.handle.net/21.15107/rcub_ibiss_4709

Harhaji-Trajković L, Kosić M, Paunović V, Ristić B, Bošnjak M, Zogović N, Mandić M, Tovilović-Kovačević G, Janjetović K, Trajković V. Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy. in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“. 2021;:8.
https://hdl.handle.net/21.15107/rcub_ibiss_4709 .

Harhaji-Trajković, Ljubica, Kosić, Milica, Paunović, Verica, Ristić, Biljana, Bošnjak, Mihajlo, Zogović, Nevena, Mandić, Miloš, Tovilović-Kovačević, Gordana, Janjetović, Kristina, Trajković, Vladimir, "Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy" in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“ (2021):8,
https://hdl.handle.net/21.15107/rcub_ibiss_4709 .

TY  - CONF
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Mirčić, Aleksandar
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Kosić, Milica
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4726
AB  - We here investigated the ability of graphene quantum dots (GQD), graphene nanoparticles with antioxidative capacity, to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). Although GQD diminished the levels of nitric oxide (NO) in both cell free condition and SNPexposed cells, NO scavengers (PTIO and uric acid), displayed only slight protection from SNP, suggesting that NO scavenging was not the main protective mechanism of GQD. Moreover, GQD significantly protected SH-SY5Y cells from neurotoxicity of light exhausted SNP, incapable of producing NO, implying the existence of protective mechanism independent of NO-scavenging. GQD lowered the increase in the concentration of hydroxyl radical (•OH) and superoxide anion (O2•−) caused by SNP both in the cell-free condition and inside cells, as well as ensuing oxidative stress and lipid peroxidation. Nonspecific antioxidants (glutathione, NAC), •OH scavenger (DMSO), and iron chelators (DTPA, BPDSA), but not superoxide dismutase, mimicked the cytoprotective activity of GQD, suggesting that GQD protect cells by neutralizing •OH generated in the presence of iron released from SNP. GQD were readily internalized by SH-SY5Y cells, while extensive washing of cells pre-incubated with GQD only partly reduced their protective activity, suggesting that GQD exerted neuroprotective effect both intra- and extracellularly. By demonstrating that GQD protect neuroblastoma cells from SNP-induced neurotoxicity by both extracellular •OH/NO scavenging and some unknown intracellular mechanism, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative and neuroinflammatory disorders associated with oxidative/nitrosative stress.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging
DO  - 10.1016/j.freeradbiomed.2021.08.167
SP  - 165
ER  - 

@conference{
author = "Ristić, Biljana and Krunić, Matija and Bošnjak, Mihajlo and Paunović, Verica and Zogović, Nevena and Tovilović-Kovačević, Gordana and Mirčić, Aleksandar and Misirkić Marjanović, Maja and Vučićević, Ljubica and Kosić, Milica and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2021",
abstract = "We here investigated the ability of graphene quantum dots (GQD), graphene nanoparticles with antioxidative capacity, to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). Although GQD diminished the levels of nitric oxide (NO) in both cell free condition and SNPexposed cells, NO scavengers (PTIO and uric acid), displayed only slight protection from SNP, suggesting that NO scavenging was not the main protective mechanism of GQD. Moreover, GQD significantly protected SH-SY5Y cells from neurotoxicity of light exhausted SNP, incapable of producing NO, implying the existence of protective mechanism independent of NO-scavenging. GQD lowered the increase in the concentration of hydroxyl radical (•OH) and superoxide anion (O2•−) caused by SNP both in the cell-free condition and inside cells, as well as ensuing oxidative stress and lipid peroxidation. Nonspecific antioxidants (glutathione, NAC), •OH scavenger (DMSO), and iron chelators (DTPA, BPDSA), but not superoxide dismutase, mimicked the cytoprotective activity of GQD, suggesting that GQD protect cells by neutralizing •OH generated in the presence of iron released from SNP. GQD were readily internalized by SH-SY5Y cells, while extensive washing of cells pre-incubated with GQD only partly reduced their protective activity, suggesting that GQD exerted neuroprotective effect both intra- and extracellularly. By demonstrating that GQD protect neuroblastoma cells from SNP-induced neurotoxicity by both extracellular •OH/NO scavenging and some unknown intracellular mechanism, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative and neuroinflammatory disorders associated with oxidative/nitrosative stress.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging",
doi = "10.1016/j.freeradbiomed.2021.08.167",
pages = "165"
}

Ristić, B., Krunić, M., Bošnjak, M., Paunović, V., Zogović, N., Tovilović-Kovačević, G., Mirčić, A., Misirkić Marjanović, M., Vučićević, L., Kosić, M., Trajković, V.,& Harhaji-Trajković, L.. (2021). Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 165.
https://doi.org/10.1016/j.freeradbiomed.2021.08.167

Ristić B, Krunić M, Bošnjak M, Paunović V, Zogović N, Tovilović-Kovačević G, Mirčić A, Misirkić Marjanović M, Vučićević L, Kosić M, Trajković V, Harhaji-Trajković L. Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:165.
doi:10.1016/j.freeradbiomed.2021.08.167 .

Ristić, Biljana, Krunić, Matija, Bošnjak, Mihajlo, Paunović, Verica, Zogović, Nevena, Tovilović-Kovačević, Gordana, Mirčić, Aleksandar, Misirkić Marjanović, Maja, Vučićević, Ljubica, Kosić, Milica, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Graphene quantum dots protect SH-SY5Y cells from SNP-induced neurotoxicity by ROS/RNS scavenging" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):165,
https://doi.org/10.1016/j.freeradbiomed.2021.08.167 . .

TY  - CONF
AU  - Stevanović, Danijela
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Paunović, Verica
AU  - Kosić, Milica
AU  - Mandić, Miloš
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4725
AB  - 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) are the most common neurotoxins used to induce experimental model of Parkinson’s disease both in vivo and in vitro. Neurotoxic action of 6-OHDA and MPP+
 is mediated by oxidative stress, mitochondrial damage and induction of apoptotic cell death. Natural disaccharide trehalose exhibits antioxidative properties and stimulates removal of damaged proteins, and thus exhibits powerful
neuroprotective effect in certain brain injury models. We investigated the effects of trehalose in 6-OHDA and MPP+
 - induced oxidative stress and neurotoxicity in human neuroblastoma SH-SY5Y cells. The effects of trehalose on the cell viability and death were assessed by MTT, crystal violet, lactate dehydrogenase assay and AnnexinV-FITC/propidium iodide staining. The production of reactive oxygen species was analyzed by flow cytometry using redox-sensitive dyes dihydrorhodamine 123 (DHR) and MitoSOX Red. Further, activation of stress-related MAP kinases, p38 and JNK were investigated by immunoblot analysis. Our study demonstrated that trehalose pretreatment significantly improved cell viability and reduced neurotoxic effect of 6-OHDA, while slightly decreased cell viability and increased neurotoxic effect of MPP+. Trehalose decreased the number of 6-OHDA-induced apoptotic cells (shown by the reduced % of Annexin V+ and AnnexinV+ PI+ cells) whereas it increased apoptosis in MPP+ treated cells. Flow
cytometric analysis of DHR and MitoSOX stained cells demonstrated that trehalose pretreatment significantly reduced 6-OHDA-triggered ROS and superoxide anion radical generation. However, in MPP+-treated neurons trehalose augmented oxidative stress and production of superoxide anion. Immunoblot analysis showed that trehalose significantly decreased p38 and JNK activation only in 6-OHDA treated cells. These results indicate that trehalose has different effects on oxidative stress induced by two different neurotoxins, 6-OHDA and MPP+, and suggests further
exploration of the mechanism of its antioxidative action.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells
DO  - 10.1016/j.freeradbiomed.2021.08.097
SP  - 94
ER  - 

@conference{
author = "Stevanović, Danijela and Vučićević, Ljubica and Misirkić Marjanović, Maja and Paunović, Verica and Kosić, Milica and Mandić, Miloš and Ristić, Biljana and Bošnjak, Mihajlo and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) are the most common neurotoxins used to induce experimental model of Parkinson’s disease both in vivo and in vitro. Neurotoxic action of 6-OHDA and MPP+
 is mediated by oxidative stress, mitochondrial damage and induction of apoptotic cell death. Natural disaccharide trehalose exhibits antioxidative properties and stimulates removal of damaged proteins, and thus exhibits powerful
neuroprotective effect in certain brain injury models. We investigated the effects of trehalose in 6-OHDA and MPP+
 - induced oxidative stress and neurotoxicity in human neuroblastoma SH-SY5Y cells. The effects of trehalose on the cell viability and death were assessed by MTT, crystal violet, lactate dehydrogenase assay and AnnexinV-FITC/propidium iodide staining. The production of reactive oxygen species was analyzed by flow cytometry using redox-sensitive dyes dihydrorhodamine 123 (DHR) and MitoSOX Red. Further, activation of stress-related MAP kinases, p38 and JNK were investigated by immunoblot analysis. Our study demonstrated that trehalose pretreatment significantly improved cell viability and reduced neurotoxic effect of 6-OHDA, while slightly decreased cell viability and increased neurotoxic effect of MPP+. Trehalose decreased the number of 6-OHDA-induced apoptotic cells (shown by the reduced % of Annexin V+ and AnnexinV+ PI+ cells) whereas it increased apoptosis in MPP+ treated cells. Flow
cytometric analysis of DHR and MitoSOX stained cells demonstrated that trehalose pretreatment significantly reduced 6-OHDA-triggered ROS and superoxide anion radical generation. However, in MPP+-treated neurons trehalose augmented oxidative stress and production of superoxide anion. Immunoblot analysis showed that trehalose significantly decreased p38 and JNK activation only in 6-OHDA treated cells. These results indicate that trehalose has different effects on oxidative stress induced by two different neurotoxins, 6-OHDA and MPP+, and suggests further
exploration of the mechanism of its antioxidative action.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells",
doi = "10.1016/j.freeradbiomed.2021.08.097",
pages = "94"
}

Stevanović, D., Vučićević, L., Misirkić Marjanović, M., Paunović, V., Kosić, M., Mandić, M., Ristić, B., Bošnjak, M., Janjetović, K., Zogović, N., Tovilović-Kovačević, G., Harhaji-Trajković, L.,& Trajković, V.. (2021). The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 94.
https://doi.org/10.1016/j.freeradbiomed.2021.08.097

Stevanović D, Vučićević L, Misirkić Marjanović M, Paunović V, Kosić M, Mandić M, Ristić B, Bošnjak M, Janjetović K, Zogović N, Tovilović-Kovačević G, Harhaji-Trajković L, Trajković V. The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:94.
doi:10.1016/j.freeradbiomed.2021.08.097 .

Stevanović, Danijela, Vučićević, Ljubica, Misirkić Marjanović, Maja, Paunović, Verica, Kosić, Milica, Mandić, Miloš, Ristić, Biljana, Bošnjak, Mihajlo, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):94,
https://doi.org/10.1016/j.freeradbiomed.2021.08.097 . .

TY  - CONF
AU  - Despotović, Ana
AU  - Zogović, Nevena
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Tovilović-Kovačević, Gordana
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4723
AB  - Glioblastoma multiforme (GBM) represents the most common and aggressive brain tumor that still lacks effective treatment options. Tumorigenesis and progression of GBM is tightly connected with over-activation of PI3K/Akt pathway, as well as with perturbed reactive oxygen species (ROS) generation in tumor cells and microenvironment. Breaking the redox balance within the tumor cells by enhancing ROS production is one of the proposed strategies for the treatment of malignancies. The aim of this study was to investigate potential antiglioma effect of ascorbic acid (AA) and menadione (MD) combination (AA+MD), the well-known oxidative stress inducer, and determine the interplay between Akt kinase activity and ROS generation in AA+MD-treated human U251 glioblastoma cells. To this end, U251 cells were treated with AA, MD and AA+MD, in the presence or absence of antioxidant N-acetylcysteine (NAC) or selective Akt inhibitor 10-DEBC hydrochloride (DEBC). Cell viability was assessed using crystal violet and MTT assays, ROS production was evaluated by flow cytometry of dihydrorhodamine-labeled cells, while Akt activity was determined using immunoblot. In contrast to AA and MD alone, combined treatment significantly decreased viability of U251 cells. The prominent toxicity of AA+MD was accompanied by an increase in ROS generation and Akt inhibition. ROS scavenger NAC diminished both Akt inhibition and cytotoxic effect of AA+MD, suggesting that Akt inactivation and cell death induced by AA+MD are ROS-dependent. Additionally, specific Akt inhibitor DEBC further enhanced death of U251 cells and elevated AA+MD-induced ROS production. Collectively, these results suggest that PI3K/Akt serves as pro-survival pathway, and its abolishing due to excessive ROS accumulation leads to glioblastoma cell death. Further, a pro-survival role of PI3K/Akt might encompass ROS removal. In conclusion, treatment with AA and MD, particularly in combination with Akt-targeted therapy, has great potential in combating GBM which is worthy of further investigation.
PB  - Amsterdam : Elsevier
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt
DO  - 10.1016/j.freeradbiomed.2021.08.072
SP  - 69
ER  - 

@conference{
author = "Despotović, Ana and Zogović, Nevena and Trajković, Vladimir and Harhaji-Trajković, Ljubica and Tovilović-Kovačević, Gordana",
year = "2021",
abstract = "Glioblastoma multiforme (GBM) represents the most common and aggressive brain tumor that still lacks effective treatment options. Tumorigenesis and progression of GBM is tightly connected with over-activation of PI3K/Akt pathway, as well as with perturbed reactive oxygen species (ROS) generation in tumor cells and microenvironment. Breaking the redox balance within the tumor cells by enhancing ROS production is one of the proposed strategies for the treatment of malignancies. The aim of this study was to investigate potential antiglioma effect of ascorbic acid (AA) and menadione (MD) combination (AA+MD), the well-known oxidative stress inducer, and determine the interplay between Akt kinase activity and ROS generation in AA+MD-treated human U251 glioblastoma cells. To this end, U251 cells were treated with AA, MD and AA+MD, in the presence or absence of antioxidant N-acetylcysteine (NAC) or selective Akt inhibitor 10-DEBC hydrochloride (DEBC). Cell viability was assessed using crystal violet and MTT assays, ROS production was evaluated by flow cytometry of dihydrorhodamine-labeled cells, while Akt activity was determined using immunoblot. In contrast to AA and MD alone, combined treatment significantly decreased viability of U251 cells. The prominent toxicity of AA+MD was accompanied by an increase in ROS generation and Akt inhibition. ROS scavenger NAC diminished both Akt inhibition and cytotoxic effect of AA+MD, suggesting that Akt inactivation and cell death induced by AA+MD are ROS-dependent. Additionally, specific Akt inhibitor DEBC further enhanced death of U251 cells and elevated AA+MD-induced ROS production. Collectively, these results suggest that PI3K/Akt serves as pro-survival pathway, and its abolishing due to excessive ROS accumulation leads to glioblastoma cell death. Further, a pro-survival role of PI3K/Akt might encompass ROS removal. In conclusion, treatment with AA and MD, particularly in combination with Akt-targeted therapy, has great potential in combating GBM which is worthy of further investigation.",
publisher = "Amsterdam : Elsevier",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt",
doi = "10.1016/j.freeradbiomed.2021.08.072",
pages = "69"
}

Despotović, A., Zogović, N., Trajković, V., Harhaji-Trajković, L.,& Tovilović-Kovačević, G.. (2021). Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Amsterdam : Elsevier., 69.
https://doi.org/10.1016/j.freeradbiomed.2021.08.072

Despotović A, Zogović N, Trajković V, Harhaji-Trajković L, Tovilović-Kovačević G. Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:69.
doi:10.1016/j.freeradbiomed.2021.08.072 .

Despotović, Ana, Zogović, Nevena, Trajković, Vladimir, Harhaji-Trajković, Ljubica, Tovilović-Kovačević, Gordana, "Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):69,
https://doi.org/10.1016/j.freeradbiomed.2021.08.072 . .

TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0891584921007760
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4655
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•-), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy-limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.
VL  - 177
DO  - 10.1016/j.freeradbiomed.2021.10.025
SP  - 167
EP  - 180
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović-Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•-), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy-limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.",
volume = "177",
doi = "10.1016/j.freeradbiomed.2021.10.025",
pages = "167-180"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Marković, Z., Todorović-Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.. in Free Radical Biology and Medicine
Elsevier Inc.., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Mirčić A, Marković Z, Todorović-Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković O, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović-Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death." in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - CONF
AU  - Mićić, Bojana
AU  - Radovanović, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Teofilović, Ana
AU  - Gligorovska, Ljupka
AU  - Vojnović-Milutinović, Danijela
AU  - Đorđević, Ana
AU  - Ignjatović, Đurđica
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4718
AB  - Fructose intake is associated with low-grade inflammation and increased oxidative
stress. Among long chain polyunsaturated fatty acids (LC-PUFAs), Ω-6 are recognized as a
contributing factor to inflammation, while Ω-3 LC-PUFAs are considered as functional foods with
beneficial effects, including inhibition of pro-inflammatory pathways. The aim of this study was to
analyze combined effects of physiologically relevant LC-PUFAs and fructose on inflammation and
antioxidant enzymes in the in vitro model of vascular endothelial cells. We examined the effects
of 0.5 mM fructose, alone and in combination with Ω-6 (arachidonic (AA) and linoleic (LA)) and
Ω-3 (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) LC-PUFAs on expression of pro-
inflammatory cytokines (tumor necrosis factor α (TNFα) and interleukin 6 (IL6)) in EA.hy926 cells.
The protein levels of nuclear factor-κB (NF-κB) and IB, as well as its phosphorylation, together
with superoxide dismutase (SOD) 1 and 2, catalase and glutathione reductase (GR) were also
analyzed. Total ROS amounts were determined using flow cytometric analysis of cells stained
with redox sensitive dihydrorhodamine 123 dye. The results showed that treatment of cells with
fructose increased TNFα and decreased IL6 mRNA levels. Additional treatment with LA, DHA
and EPA reduced TNFα and led to further decrease of IL6 expression. The observed changes
were not associated with NFB activation. All examined enzymes were unchanged after fructose
treatment, while GR was increased by LC-PUFA addition. SOD2 was reduced in cells treated
with AA, LA and EPA, while increased ROS amounts were observed with AA, DHA and EPA. This
was also evident in combined treatment with fructose. These preliminary results suggest that
LC-PUFAs, besides effect on pro-inflammatory cytokines, reduce SOD2 levels and increase ROS.
The increased levels of ROS could stimulate production of PUFA-derived peroxides, which in
GSH-enriched environment might be converted into anti-inflammatory derivatives, additionally
suppressing inflammation in fructose treated endothelial cells
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells
DO  - 10.1016/j.freeradbiomed.2021.08.092
SP  - S79
ER  - 

@conference{
author = "Mićić, Bojana and Radovanović, Marina and Tovilović-Kovačević, Gordana and Teofilović, Ana and Gligorovska, Ljupka and Vojnović-Milutinović, Danijela and Đorđević, Ana and Ignjatović, Đurđica",
year = "2021",
abstract = "Fructose intake is associated with low-grade inflammation and increased oxidative
stress. Among long chain polyunsaturated fatty acids (LC-PUFAs), Ω-6 are recognized as a
contributing factor to inflammation, while Ω-3 LC-PUFAs are considered as functional foods with
beneficial effects, including inhibition of pro-inflammatory pathways. The aim of this study was to
analyze combined effects of physiologically relevant LC-PUFAs and fructose on inflammation and
antioxidant enzymes in the in vitro model of vascular endothelial cells. We examined the effects
of 0.5 mM fructose, alone and in combination with Ω-6 (arachidonic (AA) and linoleic (LA)) and
Ω-3 (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) LC-PUFAs on expression of pro-
inflammatory cytokines (tumor necrosis factor α (TNFα) and interleukin 6 (IL6)) in EA.hy926 cells.
The protein levels of nuclear factor-κB (NF-κB) and IB, as well as its phosphorylation, together
with superoxide dismutase (SOD) 1 and 2, catalase and glutathione reductase (GR) were also
analyzed. Total ROS amounts were determined using flow cytometric analysis of cells stained
with redox sensitive dihydrorhodamine 123 dye. The results showed that treatment of cells with
fructose increased TNFα and decreased IL6 mRNA levels. Additional treatment with LA, DHA
and EPA reduced TNFα and led to further decrease of IL6 expression. The observed changes
were not associated with NFB activation. All examined enzymes were unchanged after fructose
treatment, while GR was increased by LC-PUFA addition. SOD2 was reduced in cells treated
with AA, LA and EPA, while increased ROS amounts were observed with AA, DHA and EPA. This
was also evident in combined treatment with fructose. These preliminary results suggest that
LC-PUFAs, besides effect on pro-inflammatory cytokines, reduce SOD2 levels and increase ROS.
The increased levels of ROS could stimulate production of PUFA-derived peroxides, which in
GSH-enriched environment might be converted into anti-inflammatory derivatives, additionally
suppressing inflammation in fructose treated endothelial cells",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells",
doi = "10.1016/j.freeradbiomed.2021.08.092",
pages = "S79"
}

Mićić, B., Radovanović, M., Tovilović-Kovačević, G., Teofilović, A., Gligorovska, L., Vojnović-Milutinović, D., Đorđević, A.,& Ignjatović, Đ.. (2021). Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., S79.
https://doi.org/10.1016/j.freeradbiomed.2021.08.092

Mićić B, Radovanović M, Tovilović-Kovačević G, Teofilović A, Gligorovska L, Vojnović-Milutinović D, Đorđević A, Ignjatović Đ. Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:S79.
doi:10.1016/j.freeradbiomed.2021.08.092 .

Mićić, Bojana, Radovanović, Marina, Tovilović-Kovačević, Gordana, Teofilović, Ana, Gligorovska, Ljupka, Vojnović-Milutinović, Danijela, Đorđević, Ana, Ignjatović, Đurđica, "Potentiation of polyunsaturated fatty acids anti-inflammatory action through redox signaling in fructose-treated endothelial cells" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):S79,
https://doi.org/10.1016/j.freeradbiomed.2021.08.092 . .

TY  - CONF
AU  - Pergal, Marija
AU  - Brkljačić, Jelena
AU  - Tovilović-Kovačević, Gordana
AU  - Špirkova, Milena
AU  - Kodranov, Igor
AU  - Manojlović, Dragan
AU  - Knežević, Nenad
PY  - 2021
UR  - http://www.socphyschemserb.org/sr/publikacije/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5732
AB  - Surface characteristics and biocompatibility of new nanocomposites based on polyurethane network
and mesoporous silica nanoparticles (PUMSNs) were investigated. Surface topography and
roughness coefficient were studied by AFM. Biocompatibility with endothelial cells and cytotoxicity
of the PUNs were assessed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium
bromide) and cell adhesion assays. The addition of MSNs into polyurethane network led to
improvement of surface properties, as well as exhibited promising characteristics regarding adhesion
of cells, toward potential application in coating for medical devices.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings:the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction: Physical Chemistry 2021. Vol. 2; 2021 Sep 20-24; Belgrade, Serbia
T1  - Cell adhesion characteristics of polyurethane-mesoporous silica nanoparticle composite materials
SP  - 480
EP  - 482
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5732
ER  - 

@conference{
author = "Pergal, Marija and Brkljačić, Jelena and Tovilović-Kovačević, Gordana and Špirkova, Milena and Kodranov, Igor and Manojlović, Dragan and Knežević, Nenad",
year = "2021",
abstract = "Surface characteristics and biocompatibility of new nanocomposites based on polyurethane network
and mesoporous silica nanoparticles (PUMSNs) were investigated. Surface topography and
roughness coefficient were studied by AFM. Biocompatibility with endothelial cells and cytotoxicity
of the PUNs were assessed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium
bromide) and cell adhesion assays. The addition of MSNs into polyurethane network led to
improvement of surface properties, as well as exhibited promising characteristics regarding adhesion
of cells, toward potential application in coating for medical devices.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings:the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction: Physical Chemistry 2021. Vol. 2; 2021 Sep 20-24; Belgrade, Serbia",
title = "Cell adhesion characteristics of polyurethane-mesoporous silica nanoparticle composite materials",
pages = "480-482",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5732"
}

Pergal, M., Brkljačić, J., Tovilović-Kovačević, G., Špirkova, M., Kodranov, I., Manojlović, D.,& Knežević, N.. (2021). Cell adhesion characteristics of polyurethane-mesoporous silica nanoparticle composite materials. in Proceedings:the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction: Physical Chemistry 2021. Vol. 2; 2021 Sep 20-24; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 480-482.
https://hdl.handle.net/21.15107/rcub_ibiss_5732

Pergal M, Brkljačić J, Tovilović-Kovačević G, Špirkova M, Kodranov I, Manojlović D, Knežević N. Cell adhesion characteristics of polyurethane-mesoporous silica nanoparticle composite materials. in Proceedings:the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction: Physical Chemistry 2021. Vol. 2; 2021 Sep 20-24; Belgrade, Serbia. 2021;:480-482.
https://hdl.handle.net/21.15107/rcub_ibiss_5732 .

Pergal, Marija, Brkljačić, Jelena, Tovilović-Kovačević, Gordana, Špirkova, Milena, Kodranov, Igor, Manojlović, Dragan, Knežević, Nenad, "Cell adhesion characteristics of polyurethane-mesoporous silica nanoparticle composite materials" in Proceedings:the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction: Physical Chemistry 2021. Vol. 2; 2021 Sep 20-24; Belgrade, Serbia (2021):480-482,
https://hdl.handle.net/21.15107/rcub_ibiss_5732 .

TY  - JOUR
AU  - Pergal, Marija V.
AU  - Brkljačić, Jelena
AU  - Tovilović-Kovačević, Gordana
AU  - Špírkova, Milena
AU  - Kodranov, Igor D.
AU  - Manojlović, Dragan D.
AU  - Ostojić, Sanja
AU  - Knežević, Nikola Ž.
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4161
AB  - Novel polyurethane nanocomposite (PUN) materials containing different surface-functionalized mesoporous silica nanoparticles (MSNs) were prepared by in situ polymerization methodology. Polyurethane network was formed from poly (dimethylsiloxane)-based macrodiol (PDMS), 4, 4′ -methylenediphenyldiisocyanate (MDI), and hyperbranched polyester of the second pseudo-generation (BH-20; used as crosslinking agent). PU and PU/MSN nanocomposites contained equal ratios of soft PDMS and hard MDI-BH-20 segments. Non-functionalized and surface-functionalized (with 3-(trihydroxysilyl) propyl methylphosphonate (FOMSN) and 2-[methoxy (polyethyleneoxy) 6-9propyl] trimethoxysilane (PEGMSN)) MSNs were used as the nanofillers at a concentration of 1 wt%. Prepared materials were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), nanoindentation, equilibrium swelling and water absorption measurements. Characteristics of the prepared PUNs when in contact with a biological environment were assessed through testing their biocompatibility, protein adsorption and adhesion of endothelial cells. The favourable influence of MSNs on the physico-chemical and biological characteristics of these novel PUN materials was identified, which evidences their vast applicability potential as coatings for medical devices and implants.
PB  - Elsevier
T2  - Progress in Organic Coatings
T1  - Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites
VL  - 151
DO  - 10.1016/j.porgcoat.2020.106049
SP  - 106049
ER  - 

@article{
author = "Pergal, Marija V. and Brkljačić, Jelena and Tovilović-Kovačević, Gordana and Špírkova, Milena and Kodranov, Igor D. and Manojlović, Dragan D. and Ostojić, Sanja and Knežević, Nikola Ž.",
year = "2021",
abstract = "Novel polyurethane nanocomposite (PUN) materials containing different surface-functionalized mesoporous silica nanoparticles (MSNs) were prepared by in situ polymerization methodology. Polyurethane network was formed from poly (dimethylsiloxane)-based macrodiol (PDMS), 4, 4′ -methylenediphenyldiisocyanate (MDI), and hyperbranched polyester of the second pseudo-generation (BH-20; used as crosslinking agent). PU and PU/MSN nanocomposites contained equal ratios of soft PDMS and hard MDI-BH-20 segments. Non-functionalized and surface-functionalized (with 3-(trihydroxysilyl) propyl methylphosphonate (FOMSN) and 2-[methoxy (polyethyleneoxy) 6-9propyl] trimethoxysilane (PEGMSN)) MSNs were used as the nanofillers at a concentration of 1 wt%. Prepared materials were characterized by Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), nanoindentation, equilibrium swelling and water absorption measurements. Characteristics of the prepared PUNs when in contact with a biological environment were assessed through testing their biocompatibility, protein adsorption and adhesion of endothelial cells. The favourable influence of MSNs on the physico-chemical and biological characteristics of these novel PUN materials was identified, which evidences their vast applicability potential as coatings for medical devices and implants.",
publisher = "Elsevier",
journal = "Progress in Organic Coatings",
title = "Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites",
volume = "151",
doi = "10.1016/j.porgcoat.2020.106049",
pages = "106049"
}

Pergal, M. V., Brkljačić, J., Tovilović-Kovačević, G., Špírkova, M., Kodranov, I. D., Manojlović, D. D., Ostojić, S.,& Knežević, N. Ž.. (2021). Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites. in Progress in Organic Coatings
Elsevier., 151, 106049.
https://doi.org/10.1016/j.porgcoat.2020.106049

Pergal MV, Brkljačić J, Tovilović-Kovačević G, Špírkova M, Kodranov ID, Manojlović DD, Ostojić S, Knežević NŽ. Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites. in Progress in Organic Coatings. 2021;151:106049.
doi:10.1016/j.porgcoat.2020.106049 .

Pergal, Marija V., Brkljačić, Jelena, Tovilović-Kovačević, Gordana, Špírkova, Milena, Kodranov, Igor D., Manojlović, Dragan D., Ostojić, Sanja, Knežević, Nikola Ž., "Effect of mesoporous silica nanoparticles on the properties of polyurethane network composites" in Progress in Organic Coatings, 151 (2021):106049,
https://doi.org/10.1016/j.porgcoat.2020.106049 . .

TY  - CHAP
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Krstić Milošević, Dijana
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/123456789/3896
AB  - Gentianaceae have a long history of use as traditional remedies for treatment of various ailments. The medicinal properties of crude herbal drug are attributed to bitter glycosides, flavonoids, and xanthones, the main plant secondary metabolites. These plant-derived molecules, especially naturally occurring xanthones, possess a broad spectrum of bioactivity like anticarcinogenic, antimicrobial, neuroprotective, antidiabetic, cardio-protective. The most of Gentianaceae species are rare and endangered by uncontrolled overharvesting and influences of various environmental factors (habitat loss, climate change, and invasive species spreading). Decline of Gentianaceae species poses a high risk to the loss of enormous diversity of potentially bioactive compounds. In this chapter we will summarize pharmacological activities of identified secondary metabolites from endangered species belonging to four Gentianaceae genera (Gentiana, Gentianella, Centaurium, Swertia), as well as importance of biodiversity conservation in context of their biotherapeutic potential.
PB  - Academic Press
T2  - Biodiversity and Biomedicine Our Future
T1  - Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics
DO  - 10.1016/B978-0-12-819541-3.00019-0
SP  - 335
EP  - 384
ER  - 

@inbook{
author = "Tovilović-Kovačević, Gordana and Zogović, Nevena and Krstić Milošević, Dijana",
year = "2020",
abstract = "Gentianaceae have a long history of use as traditional remedies for treatment of various ailments. The medicinal properties of crude herbal drug are attributed to bitter glycosides, flavonoids, and xanthones, the main plant secondary metabolites. These plant-derived molecules, especially naturally occurring xanthones, possess a broad spectrum of bioactivity like anticarcinogenic, antimicrobial, neuroprotective, antidiabetic, cardio-protective. The most of Gentianaceae species are rare and endangered by uncontrolled overharvesting and influences of various environmental factors (habitat loss, climate change, and invasive species spreading). Decline of Gentianaceae species poses a high risk to the loss of enormous diversity of potentially bioactive compounds. In this chapter we will summarize pharmacological activities of identified secondary metabolites from endangered species belonging to four Gentianaceae genera (Gentiana, Gentianella, Centaurium, Swertia), as well as importance of biodiversity conservation in context of their biotherapeutic potential.",
publisher = "Academic Press",
journal = "Biodiversity and Biomedicine Our Future",
booktitle = "Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics",
doi = "10.1016/B978-0-12-819541-3.00019-0",
pages = "335-384"
}

Tovilović-Kovačević, G., Zogović, N.,& Krstić Milošević, D.. (2020). Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics. in Biodiversity and Biomedicine Our Future
Academic Press., 335-384.
https://doi.org/10.1016/B978-0-12-819541-3.00019-0

Tovilović-Kovačević G, Zogović N, Krstić Milošević D. Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics. in Biodiversity and Biomedicine Our Future. 2020;:335-384.
doi:10.1016/B978-0-12-819541-3.00019-0 .

Tovilović-Kovačević, Gordana, Zogović, Nevena, Krstić Milošević, Dijana, "Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics" in Biodiversity and Biomedicine Our Future (2020):335-384,
https://doi.org/10.1016/B978-0-12-819541-3.00019-0 . .

TY  - CONF
AU  - Gligorovska, Ljupka
AU  - Ljumović, Kristina
AU  - Ignjatović, Đurđica
AU  - Tovilović-Kovačević, Gordana
AU  - Đorđević, Ana
PY  - 2020
UR  - https://sites.google.com/view/costmeetingbelgrade/home
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3992
AB  - Modern lifestyle, characterized by increased consumption of fructose-enriched beverages, can lead to obesity, type 2 diabetes and cardiovascular diseases. Since increased fructose intake is often associated with chronic low-grade inflammation and increased oxidative stress in various tissues, the aim was to investigate the level of inflammation and antioxidant protection in endothelial, neuroblastoma and preadipocyte cell lines treated with fructose. We examined the effects of 4-hour treatment with different concentrations of fructose (0.5 mM, 2.5 mM and 10 mM) on gene expression of pro-inflammatory cytokines (tumor necrosis factor α (TNFα), interleukin (IL) 1β and 6) in endothelial (EA.hy926), neuroblastoma (SH-SY5Y) and differentiated preadipocyte (3T3-F442A) cells. The protein levels of nuclear factor-κB (NF-κB), IκB, superoxide dismutase (SOD) 1 and 2, catalase, glutathione reductase and glutathione S-transferase, were also analyzed. In endothelial cells, 0.5 mM and 2.5 mM fructose treatment caused significant increase of TNFα mRNA level, while in SH-SY5Y and differentiated 3T3-F442A cells, IL-6 mRNA level was elevated after 0.5 mM fructose treatment. Although fructose increased pro-inflammatory cytokines in cell-type and dose-specific manner, decreased IκB protein level was detected only in adipocytes regardless of the dose. Finally, among all examined antioxidant enzymes, only SOD2 was significantly reduced in all cell types upon 2.5 mM fructose treatment. These preliminary results show that the effects of fructose on inflammation and antioxidant enzymes are both cell-type and dose specific. A marked decrease in the levels of SOD2, observed in all examined cells, can be associated with lower antioxidative defense under moderate fructose concentration.
PB  - University of Belgrade: Faculty of Pharmacy
C3  - Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts
T1  - Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment
SP  - 36
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3992
ER  - 

@conference{
author = "Gligorovska, Ljupka and Ljumović, Kristina and Ignjatović, Đurđica and Tovilović-Kovačević, Gordana and Đorđević, Ana",
year = "2020",
abstract = "Modern lifestyle, characterized by increased consumption of fructose-enriched beverages, can lead to obesity, type 2 diabetes and cardiovascular diseases. Since increased fructose intake is often associated with chronic low-grade inflammation and increased oxidative stress in various tissues, the aim was to investigate the level of inflammation and antioxidant protection in endothelial, neuroblastoma and preadipocyte cell lines treated with fructose. We examined the effects of 4-hour treatment with different concentrations of fructose (0.5 mM, 2.5 mM and 10 mM) on gene expression of pro-inflammatory cytokines (tumor necrosis factor α (TNFα), interleukin (IL) 1β and 6) in endothelial (EA.hy926), neuroblastoma (SH-SY5Y) and differentiated preadipocyte (3T3-F442A) cells. The protein levels of nuclear factor-κB (NF-κB), IκB, superoxide dismutase (SOD) 1 and 2, catalase, glutathione reductase and glutathione S-transferase, were also analyzed. In endothelial cells, 0.5 mM and 2.5 mM fructose treatment caused significant increase of TNFα mRNA level, while in SH-SY5Y and differentiated 3T3-F442A cells, IL-6 mRNA level was elevated after 0.5 mM fructose treatment. Although fructose increased pro-inflammatory cytokines in cell-type and dose-specific manner, decreased IκB protein level was detected only in adipocytes regardless of the dose. Finally, among all examined antioxidant enzymes, only SOD2 was significantly reduced in all cell types upon 2.5 mM fructose treatment. These preliminary results show that the effects of fructose on inflammation and antioxidant enzymes are both cell-type and dose specific. A marked decrease in the levels of SOD2, observed in all examined cells, can be associated with lower antioxidative defense under moderate fructose concentration.",
publisher = "University of Belgrade: Faculty of Pharmacy",
journal = "Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts",
title = "Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment",
pages = "36",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3992"
}

Gligorovska, L., Ljumović, K., Ignjatović, Đ., Tovilović-Kovačević, G.,& Đorđević, A.. (2020). Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment. in Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts
University of Belgrade: Faculty of Pharmacy., 36.
https://hdl.handle.net/21.15107/rcub_ibiss_3992

Gligorovska L, Ljumović K, Ignjatović Đ, Tovilović-Kovačević G, Đorđević A. Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment. in Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts. 2020;:36.
https://hdl.handle.net/21.15107/rcub_ibiss_3992 .

Gligorovska, Ljupka, Ljumović, Kristina, Ignjatović, Đurđica, Tovilović-Kovačević, Gordana, Đorđević, Ana, "Inflammatory and antioxidative response of different cell lines after in vitro fructose treatment" in Nutraceuticals in balancing redox status in ageing and age-related diseases, Book of Abstracts (2020):36,
https://hdl.handle.net/21.15107/rcub_ibiss_3992 .

TY  - CONF
AU  - Jeremić, Marija
AU  - Jovanović, Maja
AU  - Dulović, Marija
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Vukojević, Milica
AU  - Kostić, Vladimir
AU  - Marković, Ivanka
AU  - Trajković, Vladimir
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6342
AB  - Alpha-synuclein (ASYN) is regarded as one of the key culprits in pathogenesis of synucleinopathies, including Parkinson’s disease, and impaired regulation of autophagy is associated with the ASYN aggregation. Autophagy is regulated by complex mechanisms, including AMP activated protein kinase (AMPK), a key energy sensor regulating cellular metabolism to maintain energy homeostasis. The aim of our study was to investigate the role of AMPK and autophagy in neurotoxic effect of secreted ASYN, as well as dopamine-modified and nitrated recombinant wild-type ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y cells. The culture supernatant from neuroblastoma cells stably expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed by immunoblot, following lyophilisation. The CM, as well as recombinant dopamine-modified or nitrated ASYN, all reduced viability in differentiated SH-SY5Y cells. This decrease in viability was accompanied by reduced AMPK activation, increased conversion of LC3-I to LC3-II and increase
in Beclin-1 level, as demonstrated by immunoblot. Pharmacological activators of AMPK and autophagy (metformin and AICAR) significantly increased the cells’ viability in the presence of CM and modified ASYN forms. Pharmacological inhibitors of autophagy (chloroqine, bafilomycin A1 and ammonium-chloride), further reduced cell viability in the presence of extracellular ASYN. The shRNA-mediated LC3 downregulation, as well as the RNA interference-mediated knockdown of ATG7 gene, both important for autophagosome biogenesis/maturation, increased sensitivity of SH-SY5Y cells to the extracellular ASYN-induced toxicity. These data demonstrate the protective role of AMPK and autophagy against the toxicity of extracellular ASYN, suggesting that their modulation may be a promising neuroprotective strategy in Parkinson’s disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein
SP  - 493
EP  - 493
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6342
ER  - 

@conference{
author = "Jeremić, Marija and Jovanović, Maja and Dulović, Marija and Tovilović-Kovačević, Gordana and Zogović, Nevena and Harhaji-Trajković, Ljubica and Vukojević, Milica and Kostić, Vladimir and Marković, Ivanka and Trajković, Vladimir",
year = "2019",
abstract = "Alpha-synuclein (ASYN) is regarded as one of the key culprits in pathogenesis of synucleinopathies, including Parkinson’s disease, and impaired regulation of autophagy is associated with the ASYN aggregation. Autophagy is regulated by complex mechanisms, including AMP activated protein kinase (AMPK), a key energy sensor regulating cellular metabolism to maintain energy homeostasis. The aim of our study was to investigate the role of AMPK and autophagy in neurotoxic effect of secreted ASYN, as well as dopamine-modified and nitrated recombinant wild-type ASYN oligomers, on retinoic acid (RA)-differentiated SH-SY5Y cells. The culture supernatant from neuroblastoma cells stably expressing wt ASYN was collected and used as conditioned medium (CM). The presence of wt ASYN in CM was confirmed by immunoblot, following lyophilisation. The CM, as well as recombinant dopamine-modified or nitrated ASYN, all reduced viability in differentiated SH-SY5Y cells. This decrease in viability was accompanied by reduced AMPK activation, increased conversion of LC3-I to LC3-II and increase
in Beclin-1 level, as demonstrated by immunoblot. Pharmacological activators of AMPK and autophagy (metformin and AICAR) significantly increased the cells’ viability in the presence of CM and modified ASYN forms. Pharmacological inhibitors of autophagy (chloroqine, bafilomycin A1 and ammonium-chloride), further reduced cell viability in the presence of extracellular ASYN. The shRNA-mediated LC3 downregulation, as well as the RNA interference-mediated knockdown of ATG7 gene, both important for autophagosome biogenesis/maturation, increased sensitivity of SH-SY5Y cells to the extracellular ASYN-induced toxicity. These data demonstrate the protective role of AMPK and autophagy against the toxicity of extracellular ASYN, suggesting that their modulation may be a promising neuroprotective strategy in Parkinson’s disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein",
pages = "493-493",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6342"
}

Jeremić, M., Jovanović, M., Dulović, M., Tovilović-Kovačević, G., Zogović, N., Harhaji-Trajković, L., Vukojević, M., Kostić, V., Marković, I.,& Trajković, V.. (2019). The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 493-493.
https://hdl.handle.net/21.15107/rcub_ibiss_6342

Jeremić M, Jovanović M, Dulović M, Tovilović-Kovačević G, Zogović N, Harhaji-Trajković L, Vukojević M, Kostić V, Marković I, Trajković V. The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:493-493.
https://hdl.handle.net/21.15107/rcub_ibiss_6342 .

Jeremić, Marija, Jovanović, Maja, Dulović, Marija, Tovilović-Kovačević, Gordana, Zogović, Nevena, Harhaji-Trajković, Ljubica, Vukojević, Milica, Kostić, Vladimir, Marković, Ivanka, Trajković, Vladimir, "The protective role of AMPK and autophagy in neurotoxicity caused by extracellular alpha-synuclein" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):493-493,
https://hdl.handle.net/21.15107/rcub_ibiss_6342 .