TY  - CONF
AU  - Stevanović, Danijela
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Mandić, Miloš
AU  - Harhaji-Trajković, Ljubica
AU  - Janjetović, Kristina
AU  - Kosić, Milica
AU  - Lalošević, Jovan
AU  - Nikolić, Miloš
AU  - Bonači-Nikolić, Branka
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/123456789/6286
AB  - Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1
cells expressing SARS-Cov2 proteins NSP5 and ORF3a.
Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital
admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured
by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time
points, whereasIL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy
markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor
p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a
in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase
of intracellular and secreted p62. This was associated with an NSP5-mediated decrease inTNF/IL-10 mRNA
and an ORF3a-mediated increase inTNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62
mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a.
Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect
SARS-CoV-induced inflammation.
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  - Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19
SP  - 76
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6286
ER  - 

@conference{
author = "Stevanović, Danijela and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Harhaji-Trajković, Ljubica and Janjetović, Kristina and Kosić, Milica and Lalošević, Jovan and Nikolić, Miloš and Bonači-Nikolić, Branka and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1
cells expressing SARS-Cov2 proteins NSP5 and ORF3a.
Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital
admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured
by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time
points, whereasIL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy
markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor
p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a
in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase
of intracellular and secreted p62. This was associated with an NSP5-mediated decrease inTNF/IL-10 mRNA
and an ORF3a-mediated increase inTNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62
mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a.
Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect
SARS-CoV-induced inflammation.",
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 = "Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19",
pages = "76",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6286"
}

Stevanović, D., Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Harhaji-Trajković, L., Janjetović, K., Kosić, M., Lalošević, J., Nikolić, M., Bonači-Nikolić, B.,& Trajković, V.. (2023). Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19. 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., 76.
https://hdl.handle.net/21.15107/rcub_ibiss_6286

Stevanović D, Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Harhaji-Trajković L, Janjetović K, Kosić M, Lalošević J, Nikolić M, Bonači-Nikolić B, Trajković V. Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:76.
https://hdl.handle.net/21.15107/rcub_ibiss_6286 .

Stevanović, Danijela, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Harhaji-Trajković, Ljubica, Janjetović, Kristina, Kosić, Milica, Lalošević, Jovan, Nikolić, Miloš, Bonači-Nikolić, Branka, Trajković, Vladimir, "Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):76,
https://hdl.handle.net/21.15107/rcub_ibiss_6286 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Janjetović, Kristina
AU  - Paunović, Verica
AU  - Stevanović, Danijela
AU  - Kosić, Milica
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/123456789/6285
AB  - Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.
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  - MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells
SP  - 56
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6285
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Janjetović, Kristina and Paunović, Verica and Stevanović, Danijela and Kosić, Milica and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.",
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 = "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells",
pages = "56",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6285"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Janjetović, K., Paunović, V., Stevanović, D., Kosić, M., Harhaji-Trajković, L.,& Trajković, V.. (2023). MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. 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., 56.
https://hdl.handle.net/21.15107/rcub_ibiss_6285

Mandić M, Misirkić Marjanović M, Vučićević L, Bošnjak M, Perović V, Ristić B, Ćirić D, Janjetović K, Paunović V, Stevanović D, Kosić M, Harhaji-Trajković L, Trajković V. MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:56.
https://hdl.handle.net/21.15107/rcub_ibiss_6285 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Janjetović, Kristina, Paunović, Verica, Stevanović, Danijela, Kosić, Milica, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):56,
https://hdl.handle.net/21.15107/rcub_ibiss_6285 .

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  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Misirkić Marjanović, Maja
AU  - Stevanović, Danijela
AU  - Janjetović, Kristina
AU  - Harhaji-Trajković, Ljubica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6102
AB  - Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced
graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as
nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumu late in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets,
suppressing their anticancer effects. A number of chemical modifications are made to GNMs to
facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the
lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabi lization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the
cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective
autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs
prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable
tumor cell identification and therapy monitoring. In this review, we explain how the characteristics
of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited
for GNM-based cancer therapy.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials
IS  - 7
VL  - 15
DO  - 10.3390/pharmaceutics15071846
SP  - 1846
ER  - 

@article{
author = "Ristić, Biljana and Bošnjak, Mihajlo and Misirkić Marjanović, Maja and Stevanović, Danijela and Janjetović, Kristina and Harhaji-Trajković, Ljubica",
year = "2023",
abstract = "Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced
graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as
nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumu late in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets,
suppressing their anticancer effects. A number of chemical modifications are made to GNMs to
facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the
lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabi lization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the
cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective
autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs
prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable
tumor cell identification and therapy monitoring. In this review, we explain how the characteristics
of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited
for GNM-based cancer therapy.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials",
number = "7",
volume = "15",
doi = "10.3390/pharmaceutics15071846",
pages = "1846"
}

Ristić, B., Bošnjak, M., Misirkić Marjanović, M., Stevanović, D., Janjetović, K.,& Harhaji-Trajković, L.. (2023). The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials. in Pharmaceutics
Basel: MDPI., 15(7), 1846.
https://doi.org/10.3390/pharmaceutics15071846

Ristić B, Bošnjak M, Misirkić Marjanović M, Stevanović D, Janjetović K, Harhaji-Trajković L. The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials. in Pharmaceutics. 2023;15(7):1846.
doi:10.3390/pharmaceutics15071846 .

Ristić, Biljana, Bošnjak, Mihajlo, Misirkić Marjanović, Maja, Stevanović, Danijela, Janjetović, Kristina, Harhaji-Trajković, Ljubica, "The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials" in Pharmaceutics, 15, no. 7 (2023):1846,
https://doi.org/10.3390/pharmaceutics15071846 . .

TY  - JOUR
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Mandić, Miloš
AU  - Stevanović, Danijela
AU  - Harhaji-Trajković, Ljubica
AU  - Lalošević, Jovan
AU  - Nikolić, Miloš
AU  - Bonači-Nikolić, Branka
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://www.mdpi.com/2073-4409/12/9/1282
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5912
AB  - As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
PB  - Basel: MDPI
T2  - Cells
T1  - Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19
IS  - 9
VL  - 12
DO  - 10.3390/cells12091282
SP  - 1282
ER  - 

@article{
author = "Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Stevanović, Danijela and Harhaji-Trajković, Ljubica and Lalošević, Jovan and Nikolić, Miloš and Bonači-Nikolić, Branka and Trajković, Vladimir",
year = "2023",
abstract = "As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19",
number = "9",
volume = "12",
doi = "10.3390/cells12091282",
pages = "1282"
}

Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Stevanović, D., Harhaji-Trajković, L., Lalošević, J., Nikolić, M., Bonači-Nikolić, B.,& Trajković, V.. (2023). Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. in Cells
Basel: MDPI., 12(9), 1282.
https://doi.org/10.3390/cells12091282

Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Stevanović D, Harhaji-Trajković L, Lalošević J, Nikolić M, Bonači-Nikolić B, Trajković V. Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. in Cells. 2023;12(9):1282.
doi:10.3390/cells12091282 .

Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Stevanović, Danijela, Harhaji-Trajković, Ljubica, Lalošević, Jovan, Nikolić, Miloš, Bonači-Nikolić, Branka, Trajković, Vladimir, "Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19" in Cells, 12, no. 9 (2023):1282,
https://doi.org/10.3390/cells12091282 . .

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  - Macut, Đuro
AU  - Opalić, Milica
AU  - Popović, Bojana
AU  - Ognjanović, Sanja
AU  - Bjekić-Macut, Jelica
AU  - Livadas, Sarantis
AU  - Petrović, Tijana
AU  - Hrnčić, Dragan
AU  - Stanojlović, Olivera
AU  - Vojnović Milutinović, Danijela
AU  - Micić, Dragan
AU  - Mastorakos, George
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6329
AB  - Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at  different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.
PB  - Bucharest: Acta Endocrinologica Foundation
T2  - Acta Endocrinologica (Bucharest)
T1  - The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update
IS  - 1
VL  - 19
DO  - 10.4183/aeb.2023.81
SP  - 81
EP  - 86
ER  - 

@article{
author = "Macut, Đuro and Opalić, Milica and Popović, Bojana and Ognjanović, Sanja and Bjekić-Macut, Jelica and Livadas, Sarantis and Petrović, Tijana and Hrnčić, Dragan and Stanojlović, Olivera and Vojnović Milutinović, Danijela and Micić, Dragan and Mastorakos, George",
year = "2023",
abstract = "Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at  different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.",
publisher = "Bucharest: Acta Endocrinologica Foundation",
journal = "Acta Endocrinologica (Bucharest)",
title = "The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update",
number = "1",
volume = "19",
doi = "10.4183/aeb.2023.81",
pages = "81-86"
}

Macut, Đ., Opalić, M., Popović, B., Ognjanović, S., Bjekić-Macut, J., Livadas, S., Petrović, T., Hrnčić, D., Stanojlović, O., Vojnović Milutinović, D., Micić, D.,& Mastorakos, G.. (2023). The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update. in Acta Endocrinologica (Bucharest)
Bucharest: Acta Endocrinologica Foundation., 19(1), 81-86.
https://doi.org/10.4183/aeb.2023.81

Macut Đ, Opalić M, Popović B, Ognjanović S, Bjekić-Macut J, Livadas S, Petrović T, Hrnčić D, Stanojlović O, Vojnović Milutinović D, Micić D, Mastorakos G. The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update. in Acta Endocrinologica (Bucharest). 2023;19(1):81-86.
doi:10.4183/aeb.2023.81 .

Macut, Đuro, Opalić, Milica, Popović, Bojana, Ognjanović, Sanja, Bjekić-Macut, Jelica, Livadas, Sarantis, Petrović, Tijana, Hrnčić, Dragan, Stanojlović, Olivera, Vojnović Milutinović, Danijela, Micić, Dragan, Mastorakos, George, "The Effects of Endocrine Disruptors on Female Gonadal Axis: an Update" in Acta Endocrinologica (Bucharest), 19, no. 1 (2023):81-86,
https://doi.org/10.4183/aeb.2023.81 . .

TY  - JOUR
AU  - Savić, Bojana
AU  - Brkljačić, Jelena
AU  - Glumac, Sofija
AU  - Šarenac, Olivera
AU  - Murphy, David
AU  - Blagojević, Duško
AU  - Japundžić-Žigon, Nina
AU  - Oreščanin-Dušić, Zorana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5759
AB  - Hypertension and its complications are a leading cause of death in the human
population. Several factors can contribute to development of hypertension, such
as genetic predisposition, high salt intake and environmental stressors, underlying
oxidative stress as one of its key trademarks. We studied the effects of increased salt
intake and chronic stress on blood pressure parameters and the activity and protein
levels of antioxidant enzymes in the heart and aorta of borderline hypertensive rats
(BHRs) with genetic susceptibility to hypertension. All animals were randomized into
four groups: (1) Wistar rats kept in baseline conditions; (2) BHRs kept in baseline
conditions; (3) BHRs drinking 0.9% saline solution; and (4) BHRs drinking 0.9% saline
solution and exposed to repeated heterotypic stress. The BHRs exhibited significantly
higher blood pressure, mitochondrial superoxide dismutase (SOD2) and catalase (CAT)
protein levels and lower glutathione peroxidase (GPx) and glutathione reductase (GR)
activities in the aorta, followed by lower CAT and GPx protein levels and higher CAT
and GR activities in the heart, compared with normotensive Wistar rats. In the BHR
aorta, high salt intake elevated CAT and GPx activities, and when combined with stress
it increased GPx and GR activities. In BHR hearts, high salt intake provoked lower CAT
activity. Adding repeated stress to salt treatment further decreased CAT activity, in
addition to Cu2+–Zn2+ superoxide dismutase (SOD1) and GR activities. The protein
level of CAT was lower, whereas SOD2 and GPx increased. Overall, our results suggest
that BHR hearts are better adapted to oxidative pressure, compared with the aorta,
when exposed to salt and stress.
PB  - Hoboken: Wiley
T2  - Experimental Physiology
T1  - Effects of salt and stress on blood pressure parameters and antioxidant enzyme function in the heart and aorta of borderline hypertensive rats
IS  - 7
VL  - 108
DO  - 10.1113/EP090714
SP  - 946
EP  - 960
ER  - 

@article{
author = "Savić, Bojana and Brkljačić, Jelena and Glumac, Sofija and Šarenac, Olivera and Murphy, David and Blagojević, Duško and Japundžić-Žigon, Nina and Oreščanin-Dušić, Zorana",
year = "2023",
abstract = "Hypertension and its complications are a leading cause of death in the human
population. Several factors can contribute to development of hypertension, such
as genetic predisposition, high salt intake and environmental stressors, underlying
oxidative stress as one of its key trademarks. We studied the effects of increased salt
intake and chronic stress on blood pressure parameters and the activity and protein
levels of antioxidant enzymes in the heart and aorta of borderline hypertensive rats
(BHRs) with genetic susceptibility to hypertension. All animals were randomized into
four groups: (1) Wistar rats kept in baseline conditions; (2) BHRs kept in baseline
conditions; (3) BHRs drinking 0.9% saline solution; and (4) BHRs drinking 0.9% saline
solution and exposed to repeated heterotypic stress. The BHRs exhibited significantly
higher blood pressure, mitochondrial superoxide dismutase (SOD2) and catalase (CAT)
protein levels and lower glutathione peroxidase (GPx) and glutathione reductase (GR)
activities in the aorta, followed by lower CAT and GPx protein levels and higher CAT
and GR activities in the heart, compared with normotensive Wistar rats. In the BHR
aorta, high salt intake elevated CAT and GPx activities, and when combined with stress
it increased GPx and GR activities. In BHR hearts, high salt intake provoked lower CAT
activity. Adding repeated stress to salt treatment further decreased CAT activity, in
addition to Cu2+–Zn2+ superoxide dismutase (SOD1) and GR activities. The protein
level of CAT was lower, whereas SOD2 and GPx increased. Overall, our results suggest
that BHR hearts are better adapted to oxidative pressure, compared with the aorta,
when exposed to salt and stress.",
publisher = "Hoboken: Wiley",
journal = "Experimental Physiology",
title = "Effects of salt and stress on blood pressure parameters and antioxidant enzyme function in the heart and aorta of borderline hypertensive rats",
number = "7",
volume = "108",
doi = "10.1113/EP090714",
pages = "946-960"
}

Savić, B., Brkljačić, J., Glumac, S., Šarenac, O., Murphy, D., Blagojević, D., Japundžić-Žigon, N.,& Oreščanin-Dušić, Z.. (2023). Effects of salt and stress on blood pressure parameters and antioxidant enzyme function in the heart and aorta of borderline hypertensive rats. in Experimental Physiology
Hoboken: Wiley., 108(7), 946-960.
https://doi.org/10.1113/EP090714

Savić B, Brkljačić J, Glumac S, Šarenac O, Murphy D, Blagojević D, Japundžić-Žigon N, Oreščanin-Dušić Z. Effects of salt and stress on blood pressure parameters and antioxidant enzyme function in the heart and aorta of borderline hypertensive rats. in Experimental Physiology. 2023;108(7):946-960.
doi:10.1113/EP090714 .

Savić, Bojana, Brkljačić, Jelena, Glumac, Sofija, Šarenac, Olivera, Murphy, David, Blagojević, Duško, Japundžić-Žigon, Nina, Oreščanin-Dušić, Zorana, "Effects of salt and stress on blood pressure parameters and antioxidant enzyme function in the heart and aorta of borderline hypertensive rats" in Experimental Physiology, 108, no. 7 (2023):946-960,
https://doi.org/10.1113/EP090714 . .

TY  - JOUR
AU  - Jeremić, Rada
AU  - Peković, Sanja
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Đelić, Marina
AU  - Dacić, Sanja
AU  - Brkić, Predrag D
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5975
AB  - A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury
IS  - 5
VL  - 24
DO  - 10.3390/ijms24054261
SP  - 4261
ER  - 

@article{
author = "Jeremić, Rada and Peković, Sanja and Lavrnja, Irena and Bjelobaba, Ivana and Đelić, Marina and Dacić, Sanja and Brkić, Predrag D",
year = "2023",
abstract = "A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury",
number = "5",
volume = "24",
doi = "10.3390/ijms24054261",
pages = "4261"
}

Jeremić, R., Peković, S., Lavrnja, I., Bjelobaba, I., Đelić, M., Dacić, S.,& Brkić, P. D.. (2023). Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury. in International Journal of Molecular Sciences
Basel: MDPI., 24(5), 4261.
https://doi.org/10.3390/ijms24054261

Jeremić R, Peković S, Lavrnja I, Bjelobaba I, Đelić M, Dacić S, Brkić PD. Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury. in International Journal of Molecular Sciences. 2023;24(5):4261.
doi:10.3390/ijms24054261 .

Jeremić, Rada, Peković, Sanja, Lavrnja, Irena, Bjelobaba, Ivana, Đelić, Marina, Dacić, Sanja, Brkić, Predrag D, "Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury" in International Journal of Molecular Sciences, 24, no. 5 (2023):4261,
https://doi.org/10.3390/ijms24054261 . .

TY  - CONF
AU  - Jeremić, Rada
AU  - Peković, Sanja
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Đelić, Marina N
AU  - Brkić, Predrag D
AU  - Dacić, Sanja
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5984
AB  - Introduction: There is growing evidence that hyperbaric oxygenation (HBO) can affect adult neural stem cells (NSCs) activity. Because the role of NSCs in recovery from brain injury is still unclear, this study examined how ablation of the sensorimotor cortex (SCA) and HBO treatment (HBOT) affect the process of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus considered to be the site of adult neurogenesis. Material and methods: Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), SCA (animals in which the right sensorimotor cortex was removed by suction ablation), and SCA+HBO (operated animals subjected to HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. The effects of HBOT were monitored by immunohistochemistry and double immunofluorescence labeling. In addition, the number of DCX+ cells was determined along the length of the SGZ in the inner and separately in the outer blade of the right dentate gyrus. Also, the total dendrite length was measured and the number of branching points, dendrite terminals, and segments were counted to quantify dendritic arborization in each neuron. Results: HBOT decreases SCA-induced loss of immature neurons, prevents reduction of dendritic branching, and increases proliferation of progenitor cells. Conclusion: Our results suggest a protective effect of HBOT by reducing the vulnerability of immature neurons in the adult DG to SCA injury.
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  - Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury
SP  - 78
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5984
ER  - 

@conference{
author = "Jeremić, Rada and Peković, Sanja and Lavrnja, Irena and Bjelobaba, Ivana and Đelić, Marina N and Brkić, Predrag D and Dacić, Sanja",
year = "2023",
abstract = "Introduction: There is growing evidence that hyperbaric oxygenation (HBO) can affect adult neural stem cells (NSCs) activity. Because the role of NSCs in recovery from brain injury is still unclear, this study examined how ablation of the sensorimotor cortex (SCA) and HBO treatment (HBOT) affect the process of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus considered to be the site of adult neurogenesis. Material and methods: Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), SCA (animals in which the right sensorimotor cortex was removed by suction ablation), and SCA+HBO (operated animals subjected to HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. The effects of HBOT were monitored by immunohistochemistry and double immunofluorescence labeling. In addition, the number of DCX+ cells was determined along the length of the SGZ in the inner and separately in the outer blade of the right dentate gyrus. Also, the total dendrite length was measured and the number of branching points, dendrite terminals, and segments were counted to quantify dendritic arborization in each neuron. Results: HBOT decreases SCA-induced loss of immature neurons, prevents reduction of dendritic branching, and increases proliferation of progenitor cells. Conclusion: Our results suggest a protective effect of HBOT by reducing the vulnerability of immature neurons in the adult DG to SCA injury.",
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 = "Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury",
pages = "78",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5984"
}

Jeremić, R., Peković, S., Lavrnja, I., Bjelobaba, I., Đelić, M. N., Brkić, P. D.,& Dacić, S.. (2023). Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 78.
https://hdl.handle.net/21.15107/rcub_ibiss_5984

Jeremić R, Peković S, Lavrnja I, Bjelobaba I, Đelić MN, Brkić PD, Dacić S. Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:78.
https://hdl.handle.net/21.15107/rcub_ibiss_5984 .

Jeremić, Rada, Peković, Sanja, Lavrnja, Irena, Bjelobaba, Ivana, Đelić, Marina N, Brkić, Predrag D, Dacić, Sanja, "Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):78,
https://hdl.handle.net/21.15107/rcub_ibiss_5984 .

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  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Jovanović, Maja
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320522001813
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35304128
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4947
AB  - We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
PB  - Elsevier Inc.
T2  - Life Sciences
T1  - MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.
VL  - 297
DO  - 10.1016/j.lfs.2022.120481
SP  - 120481
ER  - 

@article{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Jovanović, Maja and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2022",
abstract = "We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.",
publisher = "Elsevier Inc.",
journal = "Life Sciences",
title = "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.",
volume = "297",
doi = "10.1016/j.lfs.2022.120481",
pages = "120481"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Jovanović, M., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Harhaji-Trajković, L.,& Trajković, V.. (2022). MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences
Elsevier Inc.., 297, 120481.
https://doi.org/10.1016/j.lfs.2022.120481

Mandić M, Misirkić Marjanović M, Vučićević L, Jovanović M, Bošnjak M, Perović V, Ristić B, Ćirić D, Harhaji-Trajković L, Trajković V. MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences. 2022;297:120481.
doi:10.1016/j.lfs.2022.120481 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Jovanović, Maja, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells." in Life Sciences, 297 (2022):120481,
https://doi.org/10.1016/j.lfs.2022.120481 . .

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  - JOUR
AU  - Đorđević, Marija
AU  - Paunović, Verica
AU  - Jovanović Tucović, Maja
AU  - Tolić, Anja
AU  - Rajić, Jovana
AU  - Dinić, Svetlana
AU  - Uskoković, Aleksandra
AU  - Grdović, Nevena
AU  - Mihailović, Mirjana
AU  - Marković, Ivanka
AU  - Arambašić Jovanović, Jelena
AU  - Vidaković, Melita
PY  - 2022
UR  - https://www.mdpi.com/2076-3417/12/15/7938
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5102
AB  - An efficient transfection is a crucial step for the introduction of epigenetic modification in host cells, and there is a need for an optimized transfection process for individual model systems separately. Mouse pancreatic αTC1-6 cells, which act as an attractive model system for epigenetic cell reprogramming and diabetes treatment, were transiently transfected with two different transfection methods: the chemical method with polyethyleneimine (PEI) and nucleofection as a physical transfection method. Flow cytometry and fluorescent microscopy examination of GFP expression showed that transfection efficiency was affected by the size of plasmids using both transfection methods. Subsequently, the Cas9 mRNA expression confirmed successful transfection with EpiCRISPR plasmid, whereas the cell physiology remained unchanged. The adjusted nucleofection protocol for αTC1-6 cells transfected with an EpiCRISPR mix of plasmids reached 71.1% of GFP-positive transfected cells on the fifth post-transfection day and proved to be much more efficient than the 3.8% GFP-positive PEI transfected cells. Modifying the protocol, we finally specify CM-156 program and SF 4D-Nucleofector X Solutions for Amaxa™ nucleofection as a method of choice for alpha TC1-6 cell line transfection.
PB  - Basel: MDPI
T2  - Applied Sciences
T1  - Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection
IS  - 15
VL  - 12
DO  - 10.3390/app12157938
SP  - 7938
ER  - 

@article{
author = "Đorđević, Marija and Paunović, Verica and Jovanović Tucović, Maja and Tolić, Anja and Rajić, Jovana and Dinić, Svetlana and Uskoković, Aleksandra and Grdović, Nevena and Mihailović, Mirjana and Marković, Ivanka and Arambašić Jovanović, Jelena and Vidaković, Melita",
year = "2022",
abstract = "An efficient transfection is a crucial step for the introduction of epigenetic modification in host cells, and there is a need for an optimized transfection process for individual model systems separately. Mouse pancreatic αTC1-6 cells, which act as an attractive model system for epigenetic cell reprogramming and diabetes treatment, were transiently transfected with two different transfection methods: the chemical method with polyethyleneimine (PEI) and nucleofection as a physical transfection method. Flow cytometry and fluorescent microscopy examination of GFP expression showed that transfection efficiency was affected by the size of plasmids using both transfection methods. Subsequently, the Cas9 mRNA expression confirmed successful transfection with EpiCRISPR plasmid, whereas the cell physiology remained unchanged. The adjusted nucleofection protocol for αTC1-6 cells transfected with an EpiCRISPR mix of plasmids reached 71.1% of GFP-positive transfected cells on the fifth post-transfection day and proved to be much more efficient than the 3.8% GFP-positive PEI transfected cells. Modifying the protocol, we finally specify CM-156 program and SF 4D-Nucleofector X Solutions for Amaxa™ nucleofection as a method of choice for alpha TC1-6 cell line transfection.",
publisher = "Basel: MDPI",
journal = "Applied Sciences",
title = "Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection",
number = "15",
volume = "12",
doi = "10.3390/app12157938",
pages = "7938"
}

Đorđević, M., Paunović, V., Jovanović Tucović, M., Tolić, A., Rajić, J., Dinić, S., Uskoković, A., Grdović, N., Mihailović, M., Marković, I., Arambašić Jovanović, J.,& Vidaković, M.. (2022). Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection. in Applied Sciences
Basel: MDPI., 12(15), 7938.
https://doi.org/10.3390/app12157938

Đorđević M, Paunović V, Jovanović Tucović M, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, Mihailović M, Marković I, Arambašić Jovanović J, Vidaković M. Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection. in Applied Sciences. 2022;12(15):7938.
doi:10.3390/app12157938 .

Đorđević, Marija, Paunović, Verica, Jovanović Tucović, Maja, Tolić, Anja, Rajić, Jovana, Dinić, Svetlana, Uskoković, Aleksandra, Grdović, Nevena, Mihailović, Mirjana, Marković, Ivanka, Arambašić Jovanović, Jelena, Vidaković, Melita, "Nucleofection as an Efficient Method for Alpha TC1-6 Cell Line Transfection" in Applied Sciences, 12, no. 15 (2022):7938,
https://doi.org/10.3390/app12157938 . .

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  - JOUR
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Ristić, Biljana
AU  - Mirčić, Aleksandar
AU  - Bošnjak, Mihajlo
AU  - Stevanović, Danijela
AU  - Kravić-Stevović, Tamara K
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2021
UR  - https://www.sciencedirect.com/science/article/pii/S1347861321000591
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4427
AB  - We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-kinase (PI3K)-blocking autophagy inhibitor, on cancer cell death induced by simultaneous inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. 2DG/rotenone reduced ATP levels and increased mitochondrial superoxide production, causing mitochondrial swelling and necrotic death in various cancer cell lines. 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). 3MA, but not autophagy inhibition with other PI3K and lysosomal inhibitors, attenuated 2DG/rotenone-induced mitochondrial damage, oxidative stress, ATP depletion, and cell death, while antioxidant treatment mimicked its protective action. The protection was not mediated by autophagy upregulation via class I PI3K/Akt inhibition, as it was preserved in cells with genetically inhibited autophagy. 3MA increased AMPK and mTORC1 activation in energy-stressed cells, but neither AMPK nor mTORC1 inhibition reduced its cytoprotective effect. 3MA reduced JNK activation, and JNK pharmacological/genetic suppression mimicked its mitochondria-preserving and cytoprotective activity. Therefore, 3MA prevents energy stress-triggered cancer cell death through autophagy-independent mechanisms possibly involving JNK suppression and decrease of oxidative stress. Our results warrant caution when using 3MA as an autophagy inhibitor.
PB  - Kyoto : Japanese Pharmacological Society
T2  - Journal of Pharmacological Sciences
T1  - 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms
IS  - 1
VL  - 147
DO  - 10.1016/j.jphs.2021.06.003
SP  - 156
EP  - 167
ER  - 

@article{
author = "Kosić, Milica and Paunović, Verica and Ristić, Biljana and Mirčić, Aleksandar and Bošnjak, Mihajlo and Stevanović, Danijela and Kravić-Stevović, Tamara K and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2021",
abstract = "We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-kinase (PI3K)-blocking autophagy inhibitor, on cancer cell death induced by simultaneous inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. 2DG/rotenone reduced ATP levels and increased mitochondrial superoxide production, causing mitochondrial swelling and necrotic death in various cancer cell lines. 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). 3MA, but not autophagy inhibition with other PI3K and lysosomal inhibitors, attenuated 2DG/rotenone-induced mitochondrial damage, oxidative stress, ATP depletion, and cell death, while antioxidant treatment mimicked its protective action. The protection was not mediated by autophagy upregulation via class I PI3K/Akt inhibition, as it was preserved in cells with genetically inhibited autophagy. 3MA increased AMPK and mTORC1 activation in energy-stressed cells, but neither AMPK nor mTORC1 inhibition reduced its cytoprotective effect. 3MA reduced JNK activation, and JNK pharmacological/genetic suppression mimicked its mitochondria-preserving and cytoprotective activity. Therefore, 3MA prevents energy stress-triggered cancer cell death through autophagy-independent mechanisms possibly involving JNK suppression and decrease of oxidative stress. Our results warrant caution when using 3MA as an autophagy inhibitor.",
publisher = "Kyoto : Japanese Pharmacological Society",
journal = "Journal of Pharmacological Sciences",
title = "3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms",
number = "1",
volume = "147",
doi = "10.1016/j.jphs.2021.06.003",
pages = "156-167"
}

Kosić, M., Paunović, V., Ristić, B., Mirčić, A., Bošnjak, M., Stevanović, D., Kravić-Stevović, T. K., Trajković, V.,& Harhaji-Trajković, L.. (2021). 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms. in Journal of Pharmacological Sciences
Kyoto : Japanese Pharmacological Society., 147(1), 156-167.
https://doi.org/10.1016/j.jphs.2021.06.003

Kosić M, Paunović V, Ristić B, Mirčić A, Bošnjak M, Stevanović D, Kravić-Stevović TK, Trajković V, Harhaji-Trajković L. 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms. in Journal of Pharmacological Sciences. 2021;147(1):156-167.
doi:10.1016/j.jphs.2021.06.003 .

Kosić, Milica, Paunović, Verica, Ristić, Biljana, Mirčić, Aleksandar, Bošnjak, Mihajlo, Stevanović, Danijela, Kravić-Stevović, Tamara K, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms" in Journal of Pharmacological Sciences, 147, no. 1 (2021):156-167,
https://doi.org/10.1016/j.jphs.2021.06.003 . .

TY  - JOUR
AU  - Ristić, Biljana
AU  - Harhaji-Trajković, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Dakić, Ivana
AU  - Mijatović, Srđan
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/16/4145
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4431
AB  - Graphene-based nanomaterials (GNM) are plausible candidates for cancer therapeutics
and drug delivery systems. Pure graphene and graphene oxide nanoparticles, as well as graphene
quantum dots and graphene nanofibers, were all able to trigger autophagy in cancer cells through both
transcriptional and post-transcriptional mechanisms involving oxidative/endoplasmic reticulum
stress, AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein
kinase, and Toll-like receptor signaling. This was often coupled with lysosomal dysfunction and
subsequent blockade of autophagic flux, which additionally increased the accumulation of autophagy
mediators that participated in apoptotic, necrotic, or necroptotic death of cancer cells and influenced
the immune response against the tumor. In this review, we analyze molecular mechanisms and
structure–activity relationships of GNM-mediated autophagy modulation, its consequences for
cancer cell survival/death and anti-tumor immune response, and the possible implications for the
use of GNM in cancer therapy.
PB  - Basel : MDPI
T2  - Cancers
T1  - Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications
IS  - 16
VL  - 13
DO  - 10.3390/cancers13164145
SP  - 4145
ER  - 

@article{
author = "Ristić, Biljana and Harhaji-Trajković, Ljubica and Bošnjak, Mihajlo and Dakić, Ivana and Mijatović, Srđan and Trajković, Vladimir",
year = "2021",
abstract = "Graphene-based nanomaterials (GNM) are plausible candidates for cancer therapeutics
and drug delivery systems. Pure graphene and graphene oxide nanoparticles, as well as graphene
quantum dots and graphene nanofibers, were all able to trigger autophagy in cancer cells through both
transcriptional and post-transcriptional mechanisms involving oxidative/endoplasmic reticulum
stress, AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein
kinase, and Toll-like receptor signaling. This was often coupled with lysosomal dysfunction and
subsequent blockade of autophagic flux, which additionally increased the accumulation of autophagy
mediators that participated in apoptotic, necrotic, or necroptotic death of cancer cells and influenced
the immune response against the tumor. In this review, we analyze molecular mechanisms and
structure–activity relationships of GNM-mediated autophagy modulation, its consequences for
cancer cell survival/death and anti-tumor immune response, and the possible implications for the
use of GNM in cancer therapy.",
publisher = "Basel : MDPI",
journal = "Cancers",
title = "Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications",
number = "16",
volume = "13",
doi = "10.3390/cancers13164145",
pages = "4145"
}

Ristić, B., Harhaji-Trajković, L., Bošnjak, M., Dakić, I., Mijatović, S.,& Trajković, V.. (2021). Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications. in Cancers
Basel : MDPI., 13(16), 4145.
https://doi.org/10.3390/cancers13164145

Ristić B, Harhaji-Trajković L, Bošnjak M, Dakić I, Mijatović S, Trajković V. Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications. in Cancers. 2021;13(16):4145.
doi:10.3390/cancers13164145 .

Ristić, Biljana, Harhaji-Trajković, Ljubica, Bošnjak, Mihajlo, Dakić, Ivana, Mijatović, Srđan, Trajković, Vladimir, "Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications" in Cancers, 13, no. 16 (2021):4145,
https://doi.org/10.3390/cancers13164145 . .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Despotović, Ana
AU  - Stamenković, Marina
AU  - Janjetović, Kristina
PY  - 2021
UR  - http://www.ajcr.us/files/ajcr0136757.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4679
AB  - Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug.
Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin’s role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.
PB  - Madison, USA : e-Century Publishing Corporation
T2  - American Journal of Cancer Research
T1  - Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context
IS  - 11
VL  - 11
SP  - 5625
EP  - 5643
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4679
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Vučićević, Ljubica and Despotović, Ana and Stamenković, Marina and Janjetović, Kristina",
year = "2021",
abstract = "Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug.
Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin’s role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.",
publisher = "Madison, USA : e-Century Publishing Corporation",
journal = "American Journal of Cancer Research",
title = "Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context",
number = "11",
volume = "11",
pages = "5625-5643",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4679"
}

Misirkić Marjanović, M., Vučićević, L., Despotović, A., Stamenković, M.,& Janjetović, K.. (2021). Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context. in American Journal of Cancer Research
Madison, USA : e-Century Publishing Corporation., 11(11), 5625-5643.
https://hdl.handle.net/21.15107/rcub_ibiss_4679

Misirkić Marjanović M, Vučićević L, Despotović A, Stamenković M, Janjetović K. Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context. in American Journal of Cancer Research. 2021;11(11):5625-5643.
https://hdl.handle.net/21.15107/rcub_ibiss_4679 .

Misirkić Marjanović, Maja, Vučićević, Ljubica, Despotović, Ana, Stamenković, Marina, Janjetović, Kristina, "Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context" in American Journal of Cancer Research, 11, no. 11 (2021):5625-5643,
https://hdl.handle.net/21.15107/rcub_ibiss_4679 .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Sopta, Jelena
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Ivanović, Anđelija
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4090
AB  - Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium
is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑
consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment
(300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that
meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology,
and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver
high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and
the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the
increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves
the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum
and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione
and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide
dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results,
it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with
a clinical significance in surgical procedures.
PB  - Nature Publishing Group
T2  - Scientific Reports
T1  - The effects of meldonium on the acute ischemia/reperfusion liver injury in rats
IS  - 1
VL  - 11
DO  - 10.1038/s41598-020-80011-y
SP  - 1305
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Sopta, Jelena and Pavlović, Slađan and Borković Mitić, Slavica and Ivanović, Anđelija and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Đorđević, Jelena and Todorović, Zoran",
year = "2021",
abstract = "Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium
is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑
consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment
(300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that
meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology,
and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver
high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and
the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the
increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves
the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum
and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione
and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide
dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results,
it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with
a clinical significance in surgical procedures.",
publisher = "Nature Publishing Group",
journal = "Scientific Reports",
title = "The effects of meldonium on the acute ischemia/reperfusion liver injury in rats",
number = "1",
volume = "11",
doi = "10.1038/s41598-020-80011-y",
pages = "1305"
}

Đurašević, S., Stojković, M., Sopta, J., Pavlović, S., Borković Mitić, S., Ivanović, A., Jasnić, N., Tosti, T., Đurović, S., Đorđević, J.,& Todorović, Z.. (2021). The effects of meldonium on the acute ischemia/reperfusion liver injury in rats. in Scientific Reports
Nature Publishing Group., 11(1), 1305.
https://doi.org/10.1038/s41598-020-80011-y

Đurašević S, Stojković M, Sopta J, Pavlović S, Borković Mitić S, Ivanović A, Jasnić N, Tosti T, Đurović S, Đorđević J, Todorović Z. The effects of meldonium on the acute ischemia/reperfusion liver injury in rats. in Scientific Reports. 2021;11(1):1305.
doi:10.1038/s41598-020-80011-y .

Đurašević, Siniša, Stojković, Maja, Sopta, Jelena, Pavlović, Slađan, Borković Mitić, Slavica, Ivanović, Anđelija, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Đorđević, Jelena, Todorović, Zoran, "The effects of meldonium on the acute ischemia/reperfusion liver injury in rats" in Scientific Reports, 11, no. 1 (2021):1305,
https://doi.org/10.1038/s41598-020-80011-y . .

TY  - JOUR
AU  - Todorović, Zoran
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Grigorov, Ilijana
AU  - Pavlović, Slađan
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Bjekić Macut, Jelica
AU  - Thiemermann, Christoph
AU  - Đorđević, Jelena
PY  - 2021
UR  - https://www.mdpi.com/1422-0067/22/6/2798
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4162
AB  - Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.
PB  - Multidisciplinary Digital Publishing Institute
T2  - International Journal of Molecular Sciences
T1  - Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury
IS  - 6
VL  - 22
DO  - 10.3390/ijms22062798
SP  - 2798
ER  - 

@article{
author = "Todorović, Zoran and Đurašević, Siniša and Stojković, Maja and Grigorov, Ilijana and Pavlović, Slađan and Jasnić, Nebojša and Tosti, Tomislav and Bjekić Macut, Jelica and Thiemermann, Christoph and Đorđević, Jelena",
year = "2021",
abstract = "Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.",
publisher = "Multidisciplinary Digital Publishing Institute",
journal = "International Journal of Molecular Sciences",
title = "Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury",
number = "6",
volume = "22",
doi = "10.3390/ijms22062798",
pages = "2798"
}

Todorović, Z., Đurašević, S., Stojković, M., Grigorov, I., Pavlović, S., Jasnić, N., Tosti, T., Bjekić Macut, J., Thiemermann, C.,& Đorđević, J.. (2021). Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury. in International Journal of Molecular Sciences
Multidisciplinary Digital Publishing Institute., 22(6), 2798.
https://doi.org/10.3390/ijms22062798

Todorović Z, Đurašević S, Stojković M, Grigorov I, Pavlović S, Jasnić N, Tosti T, Bjekić Macut J, Thiemermann C, Đorđević J. Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury. in International Journal of Molecular Sciences. 2021;22(6):2798.
doi:10.3390/ijms22062798 .

Todorović, Zoran, Đurašević, Siniša, Stojković, Maja, Grigorov, Ilijana, Pavlović, Slađan, Jasnić, Nebojša, Tosti, Tomislav, Bjekić Macut, Jelica, Thiemermann, Christoph, Đorđević, Jelena, "Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury" in International Journal of Molecular Sciences, 22, no. 6 (2021):2798,
https://doi.org/10.3390/ijms22062798 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Pejić, Snežana
AU  - Grigorov, Ilijana
AU  - Nikolić, Gorana
AU  - Mitić-Ćulafić, Dragana
AU  - Dragićević, Milan
AU  - Đorđević, Jelena
AU  - Todorović Vukotić, Nevena
AU  - Đorđević, Neda
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Veljković, Filip
AU  - Pajović, Snežana B.
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4289
AB  - Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
PB  - MDPI
T2  - Antioxidants
T1  - Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes
IS  - 6
VL  - 10
DO  - 10.3390/antiox10060911
SP  - 911
ER  - 

@article{
author = "Đurašević, Siniša and Pejić, Snežana and Grigorov, Ilijana and Nikolić, Gorana and Mitić-Ćulafić, Dragana and Dragićević, Milan and Đorđević, Jelena and Todorović Vukotić, Nevena and Đorđević, Neda and Todorović, Ana and Drakulić, Dunja and Veljković, Filip and Pajović, Snežana B. and Todorović, Zoran",
year = "2021",
abstract = "Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes",
number = "6",
volume = "10",
doi = "10.3390/antiox10060911",
pages = "911"
}

Đurašević, S., Pejić, S., Grigorov, I., Nikolić, G., Mitić-Ćulafić, D., Dragićević, M., Đorđević, J., Todorović Vukotić, N., Đorđević, N., Todorović, A., Drakulić, D., Veljković, F., Pajović, S. B.,& Todorović, Z.. (2021). Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants
MDPI., 10(6), 911.
https://doi.org/10.3390/antiox10060911

Đurašević S, Pejić S, Grigorov I, Nikolić G, Mitić-Ćulafić D, Dragićević M, Đorđević J, Todorović Vukotić N, Đorđević N, Todorović A, Drakulić D, Veljković F, Pajović SB, Todorović Z. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants. 2021;10(6):911.
doi:10.3390/antiox10060911 .

Đurašević, Siniša, Pejić, Snežana, Grigorov, Ilijana, Nikolić, Gorana, Mitić-Ćulafić, Dragana, Dragićević, Milan, Đorđević, Jelena, Todorović Vukotić, Nevena, Đorđević, Neda, Todorović, Ana, Drakulić, Dunja, Veljković, Filip, Pajović, Snežana B., Todorović, Zoran, "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes" in Antioxidants, 10, no. 6 (2021):911,
https://doi.org/10.3390/antiox10060911 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4413
AB  - Sepsis is a life-threatening condition caused by the dysregulated and overwhelming
response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism
disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory
agent which negatively interferes with lipid metabolism by shifting energy production from fatty
acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects
of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats.
Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with
the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide
support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory
status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After
performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium
harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines
the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible
harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to
the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving
the way for discovering new therapeutic approaches.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats
IS  - 18
VL  - 22
DO  - 10.3390/ijms22189698
SP  - 9698
ER  - 

@article{
author = "Đurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Stanković, Sanja and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2021",
abstract = "Sepsis is a life-threatening condition caused by the dysregulated and overwhelming
response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism
disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory
agent which negatively interferes with lipid metabolism by shifting energy production from fatty
acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects
of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats.
Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with
the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide
support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory
status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After
performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium
harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines
the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible
harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to
the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving
the way for discovering new therapeutic approaches.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats",
number = "18",
volume = "22",
doi = "10.3390/ijms22189698",
pages = "9698"
}

Đurašević, S., Ružičić, A., Lakić, I., Tosti, T., Đurović, S., Glumac, S., Pavlović, S., Borković Mitić, S., Grigorov, I., Stanković, S., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2021). The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats. in International Journal of Molecular Sciences
Basel: MDPI., 22(18), 9698.
https://doi.org/10.3390/ijms22189698

Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pavlović S, Borković Mitić S, Grigorov I, Stanković S, Jasnić N, Đorđević J, Todorović Z. The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats. in International Journal of Molecular Sciences. 2021;22(18):9698.
doi:10.3390/ijms22189698 .

Đurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Stanković, Sanja, Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats" in International Journal of Molecular Sciences, 22, no. 18 (2021):9698,
https://doi.org/10.3390/ijms22189698 . .

TY  - JOUR
AU  - Paunović, Verica
AU  - Kosić, Milica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33383091
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4096
AB  - To sustain their proliferative and metastatic capacity, tumor cells increase the activity of energy-producing pathways and lysosomal compartment, resorting to autophagolysosomal degradation when nutrients are scarce. Consequently, large fragile lysosomes and enhanced energy metabolism may serve as targets for anticancer therapy. A simultaneous induction of energy stress (by caloric restriction and inhibition of glycolysis, oxidative phosphorylation, Krebs cycle, or amino acid/fatty acid metabolism) and lysosomal stress (by lysosomotropic detergents, vacuolar ATPase inhibitors, or cationic amphiphilic drugs) is an efficient anti-cancer strategy demonstrated in a number of studies. However, the mechanisms of lysosomal/energy stress co-amplification, apart from the protective autophagy inhibition, are poorly understood. We here summarize the established and suggest potential mechanisms and candidates for anticancer therapy based on the dual targeting of lysosomes and energy metabolism.
PB  - Elsevier BV
T2  - Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
T1  - Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy.
IS  - 4
VL  - 1868
DO  - 10.1016/j.bbamcr.2020.118944
SP  - 118944
ER  - 

@article{
author = "Paunović, Verica and Kosić, Milica and Misirkić Marjanović, Maja and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2020",
abstract = "To sustain their proliferative and metastatic capacity, tumor cells increase the activity of energy-producing pathways and lysosomal compartment, resorting to autophagolysosomal degradation when nutrients are scarce. Consequently, large fragile lysosomes and enhanced energy metabolism may serve as targets for anticancer therapy. A simultaneous induction of energy stress (by caloric restriction and inhibition of glycolysis, oxidative phosphorylation, Krebs cycle, or amino acid/fatty acid metabolism) and lysosomal stress (by lysosomotropic detergents, vacuolar ATPase inhibitors, or cationic amphiphilic drugs) is an efficient anti-cancer strategy demonstrated in a number of studies. However, the mechanisms of lysosomal/energy stress co-amplification, apart from the protective autophagy inhibition, are poorly understood. We here summarize the established and suggest potential mechanisms and candidates for anticancer therapy based on the dual targeting of lysosomes and energy metabolism.",
publisher = "Elsevier BV",
journal = "Biochimica et Biophysica Acta (BBA) - Molecular Cell Research",
title = "Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy.",
number = "4",
volume = "1868",
doi = "10.1016/j.bbamcr.2020.118944",
pages = "118944"
}

Paunović, V., Kosić, M., Misirkić Marjanović, M., Trajković, V.,& Harhaji-Trajković, L.. (2020). Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy.. in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Elsevier BV., 1868(4), 118944.
https://doi.org/10.1016/j.bbamcr.2020.118944

Paunović V, Kosić M, Misirkić Marjanović M, Trajković V, Harhaji-Trajković L. Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy.. in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2020;1868(4):118944.
doi:10.1016/j.bbamcr.2020.118944 .

Paunović, Verica, Kosić, Milica, Misirkić Marjanović, Maja, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy." in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1868, no. 4 (2020):118944,
https://doi.org/10.1016/j.bbamcr.2020.118944 . .

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 .