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  - Pantović, Aleksandar C
AU  - Krstić, Aleksandra D
AU  - Janjetović, Kristina
AU  - Kocić, Jelena S
AU  - Harhaji-Trajković, Ljubica
AU  - Bugarski, Diana S
AU  - Trajković, Vladimir S
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1064
AB  - We investigated the role of AMP-activated protein kinase (AMPK), Akt, mammalian target of rapamycin (mTOR), autophagy and their interplay in osteogenic differentiation of human dental pulp mesenchymal stem cells. The activation of various members of AMPK, Akt and mTOR signaling pathways and autophagy was analyzed by immunoblotting, while osteogenic differentiation was assessed by alkaline phosphatase staining and real-time RT-PCR/immunoblot quantification of osteocalcin, Runt-related transcription factor 2 and bone morphogenetic protein 2 mRNA and/or protein levels. Osteogenic differentiation of mesenchymal stem cells was associated with early (day 1) activation of AMPK and its target Raptor, coinciding with the inhibition of mTOR and its substrate p70S6 kinase. The early induction of autophagy was demonstrated by accumulation of autophagosome-bound LC3-11, upregulation of proautophagic,beclin-1 and a decrease in the selective autophagic target p62. This was followed by the late activation of Akt/mTOR at days 3-7 of differentiation. The RNA interference-mediated silencing of AMPK, mTOR or autophagy-essential LC3 beta, as well as the pharmacological inhibitors of AMPK (compound C), Akt (10-DEBC hydrochloride), mTOR (rapamycin) and autophagy (bafilomycin A1, chloroquine and ammonium chloride), each suppressed mesenchymal stem cell differentiation to osteoblasts. AMPK knockdown prevented early mTOR inhibition and autophagy induction, as well as late activation of Akt/mTOR signaling, while Ala inhibition suppressed mTOR activation without affecting AMPK phosphorylation. Our data indicate that AMPK controls osteogenic differentiation of human mesenchymal stem cells through both early mTOR inhibition-mediated autophagy and late activation of Akt/mTOR signaling axis. (C) 2012 Elsevier Inc. All rights reserved.
T2  - Bone
T1  - Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells
IS  - 1
VL  - 52
DO  - 10.1016/j.bone.2012.10.024
SP  - 537
EP  - 531
ER  - 

@article{
author = "Pantović, Aleksandar C and Krstić, Aleksandra D and Janjetović, Kristina and Kocić, Jelena S and Harhaji-Trajković, Ljubica and Bugarski, Diana S and Trajković, Vladimir S",
year = "2013",
abstract = "We investigated the role of AMP-activated protein kinase (AMPK), Akt, mammalian target of rapamycin (mTOR), autophagy and their interplay in osteogenic differentiation of human dental pulp mesenchymal stem cells. The activation of various members of AMPK, Akt and mTOR signaling pathways and autophagy was analyzed by immunoblotting, while osteogenic differentiation was assessed by alkaline phosphatase staining and real-time RT-PCR/immunoblot quantification of osteocalcin, Runt-related transcription factor 2 and bone morphogenetic protein 2 mRNA and/or protein levels. Osteogenic differentiation of mesenchymal stem cells was associated with early (day 1) activation of AMPK and its target Raptor, coinciding with the inhibition of mTOR and its substrate p70S6 kinase. The early induction of autophagy was demonstrated by accumulation of autophagosome-bound LC3-11, upregulation of proautophagic,beclin-1 and a decrease in the selective autophagic target p62. This was followed by the late activation of Akt/mTOR at days 3-7 of differentiation. The RNA interference-mediated silencing of AMPK, mTOR or autophagy-essential LC3 beta, as well as the pharmacological inhibitors of AMPK (compound C), Akt (10-DEBC hydrochloride), mTOR (rapamycin) and autophagy (bafilomycin A1, chloroquine and ammonium chloride), each suppressed mesenchymal stem cell differentiation to osteoblasts. AMPK knockdown prevented early mTOR inhibition and autophagy induction, as well as late activation of Akt/mTOR signaling, while Ala inhibition suppressed mTOR activation without affecting AMPK phosphorylation. Our data indicate that AMPK controls osteogenic differentiation of human mesenchymal stem cells through both early mTOR inhibition-mediated autophagy and late activation of Akt/mTOR signaling axis. (C) 2012 Elsevier Inc. All rights reserved.",
journal = "Bone",
title = "Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells",
number = "1",
volume = "52",
doi = "10.1016/j.bone.2012.10.024",
pages = "537-531"
}

Pantović, A. C., Krstić, A. D., Janjetović, K., Kocić, J. S., Harhaji-Trajković, L., Bugarski, D. S.,& Trajković, V. S.. (2013). Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. in Bone, 52(1), 537-531.
https://doi.org/10.1016/j.bone.2012.10.024

Pantović AC, Krstić AD, Janjetović K, Kocić JS, Harhaji-Trajković L, Bugarski DS, Trajković VS. Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. in Bone. 2013;52(1):537-531.
doi:10.1016/j.bone.2012.10.024 .

Pantović, Aleksandar C, Krstić, Aleksandra D, Janjetović, Kristina, Kocić, Jelena S, Harhaji-Trajković, Ljubica, Bugarski, Diana S, Trajković, Vladimir S, "Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells" in Bone, 52, no. 1 (2013):537-531,
https://doi.org/10.1016/j.bone.2012.10.024 . .

TY  - JOUR
AU  - Nesić, Dejan M
AU  - Stevanović, Darko M
AU  - Stanković, Sanja Đ
AU  - Milošević, Verica
AU  - Trajković, Vladimir S
AU  - Starčević, Vesna P.
AU  - Severs, Walter B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/997
AB  - Ghrelin is an endogenous peptide potentially useful in therapy of anorexia and other age-related metabolic disturbances. We evaluated the influence of age on the orexigenic and lipid metabolism-altering effects of ghrelin. Peripubertal, young, adult and middle-aged rats (1, 2, 7 and 12 months old, respectively) were treated with 5 daily intracerebroventricular injections of ghrelin (0.15 nmol) or saline (control). The food intake was measured daily before treatment, while white adipose tissue and serum/plasma samples for detection of lipid metabolites/hormones were collected at the end of the experiment. The values of cumulative food intake and body weight gain declined, while the white adipose tissue deposits and blood concentrations of triglycerides, cholesterol and free fatty acids all increased with age. Ghrelin significantly increased all parameters, but the stimulatory effects on body weight gain and food intake were more pronounced in peripubertal/young rats, while the increase in white adipose mass, triglyceride and low-density lipoprotein cholesterol levels was more noticeable in adult/middle-aged animals. The decrease in sensitivity to ghrelin-mediated stimulation of food intake in older animals could not be explained by alterations in ghrelin's ability to reduce anorexigenic hormones insulin and leptin. However, the higher responsiveness of aged rats to ghrelin-mediated increase in lipid metabolites was accompanied by an increase in adrenocorticotropic hormone and corticosterone levels. These results indicate that aging, while reducing sensitivity to ghrelin-mediated increase in body weight gain and food intake, might enhance the responsiveness to the stimulatory effects of ghrelin on lipid metabolites and hypothalamic-pituitary-adrenal axis activity. (C) 2013 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats
IS  - 1-3
VL  - 710
SP  - 153
EP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_997
ER  - 

@article{
author = "Nesić, Dejan M and Stevanović, Darko M and Stanković, Sanja Đ and Milošević, Verica and Trajković, Vladimir S and Starčević, Vesna P. and Severs, Walter B",
year = "2013",
abstract = "Ghrelin is an endogenous peptide potentially useful in therapy of anorexia and other age-related metabolic disturbances. We evaluated the influence of age on the orexigenic and lipid metabolism-altering effects of ghrelin. Peripubertal, young, adult and middle-aged rats (1, 2, 7 and 12 months old, respectively) were treated with 5 daily intracerebroventricular injections of ghrelin (0.15 nmol) or saline (control). The food intake was measured daily before treatment, while white adipose tissue and serum/plasma samples for detection of lipid metabolites/hormones were collected at the end of the experiment. The values of cumulative food intake and body weight gain declined, while the white adipose tissue deposits and blood concentrations of triglycerides, cholesterol and free fatty acids all increased with age. Ghrelin significantly increased all parameters, but the stimulatory effects on body weight gain and food intake were more pronounced in peripubertal/young rats, while the increase in white adipose mass, triglyceride and low-density lipoprotein cholesterol levels was more noticeable in adult/middle-aged animals. The decrease in sensitivity to ghrelin-mediated stimulation of food intake in older animals could not be explained by alterations in ghrelin's ability to reduce anorexigenic hormones insulin and leptin. However, the higher responsiveness of aged rats to ghrelin-mediated increase in lipid metabolites was accompanied by an increase in adrenocorticotropic hormone and corticosterone levels. These results indicate that aging, while reducing sensitivity to ghrelin-mediated increase in body weight gain and food intake, might enhance the responsiveness to the stimulatory effects of ghrelin on lipid metabolites and hypothalamic-pituitary-adrenal axis activity. (C) 2013 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats",
number = "1-3",
volume = "710",
pages = "153-91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_997"
}

Nesić, D. M., Stevanović, D. M., Stanković, S. Đ., Milošević, V., Trajković, V. S., Starčević, V. P.,& Severs, W. B.. (2013). Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats. in European Journal of Pharmacology, 710(1-3), 153-91.
https://hdl.handle.net/21.15107/rcub_ibiss_997

Nesić DM, Stevanović DM, Stanković SĐ, Milošević V, Trajković VS, Starčević VP, Severs WB. Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats. in European Journal of Pharmacology. 2013;710(1-3):153-91.
https://hdl.handle.net/21.15107/rcub_ibiss_997 .

Nesić, Dejan M, Stevanović, Darko M, Stanković, Sanja Đ, Milošević, Verica, Trajković, Vladimir S, Starčević, Vesna P., Severs, Walter B, "Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats" in European Journal of Pharmacology, 710, no. 1-3 (2013):153-91,
https://hdl.handle.net/21.15107/rcub_ibiss_997 .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana Z
AU  - Vilimanović, Uros
AU  - Harhaji-Trajković, Ljubica
AU  - Sumarac-Dumanović, Mirjana S
AU  - Micić, Dragan D
AU  - Bumbaširević, Vladimir Z
AU  - Trajković, Vladimir S
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1232
AB  - The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR). a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3 beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-depenclent autophagic response might sensitize glioma cells to statin-induced apoptotic death. (C) 2011 Elsevier Ltd. All rights reserved.
T2  - Pharmacological Research
T1  - Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin
IS  - 1
VL  - 65
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1232
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Tovilović-Kovačević, Gordana and Ristić, Biljana Z and Vilimanović, Uros and Harhaji-Trajković, Ljubica and Sumarac-Dumanović, Mirjana S and Micić, Dragan D and Bumbaširević, Vladimir Z and Trajković, Vladimir S",
year = "2012",
abstract = "The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR). a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3 beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-depenclent autophagic response might sensitize glioma cells to statin-induced apoptotic death. (C) 2011 Elsevier Ltd. All rights reserved.",
journal = "Pharmacological Research",
title = "Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin",
number = "1",
volume = "65",
pages = "119",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1232"
}

Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Tovilović-Kovačević, G., Ristić, B. Z., Vilimanović, U., Harhaji-Trajković, L., Sumarac-Dumanović, M. S., Micić, D. D., Bumbaširević, V. Z.,& Trajković, V. S.. (2012). Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. in Pharmacological Research, 65(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1232

Misirkić Marjanović M, Janjetović K, Vučićević L, Tovilović-Kovačević G, Ristić BZ, Vilimanović U, Harhaji-Trajković L, Sumarac-Dumanović MS, Micić DD, Bumbaširević VZ, Trajković VS. Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. in Pharmacological Research. 2012;65(1):null-119.
https://hdl.handle.net/21.15107/rcub_ibiss_1232 .

Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Tovilović-Kovačević, Gordana, Ristić, Biljana Z, Vilimanović, Uros, Harhaji-Trajković, Ljubica, Sumarac-Dumanović, Mirjana S, Micić, Dragan D, Bumbaširević, Vladimir Z, Trajković, Vladimir S, "Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin" in Pharmacological Research, 65, no. 1 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1232 .

TY  - JOUR
AU  - Misirlić-Dencić, Sonja T
AU  - Poljarević, Jelena M
AU  - Vilimanović, Uros
AU  - Bogdanović, Andrija D
AU  - Isaković, Aleksandra J
AU  - Kravić-Stevović, Tamara K
AU  - Dulović, Marija
AU  - Zogović, Nevena
AU  - Isaković, Anđelka M
AU  - Grgurić-Sipka, Sanja R
AU  - Bumbaširević, Vladimir Z
AU  - Sabo, Tibor J
AU  - Trajković, Vladimir S
AU  - Marković, Ivanka D
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1196
AB  - We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.
T2  - Chemical Research in Toxicology
T1  - Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells
IS  - 4
VL  - 25
EP  - 939
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1196
ER  - 

@article{
author = "Misirlić-Dencić, Sonja T and Poljarević, Jelena M and Vilimanović, Uros and Bogdanović, Andrija D and Isaković, Aleksandra J and Kravić-Stevović, Tamara K and Dulović, Marija and Zogović, Nevena and Isaković, Anđelka M and Grgurić-Sipka, Sanja R and Bumbaširević, Vladimir Z and Sabo, Tibor J and Trajković, Vladimir S and Marković, Ivanka D",
year = "2012",
abstract = "We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.",
journal = "Chemical Research in Toxicology",
title = "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells",
number = "4",
volume = "25",
pages = "939",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1196"
}

Misirlić-Dencić, S. T., Poljarević, J. M., Vilimanović, U., Bogdanović, A. D., Isaković, A. J., Kravić-Stevović, T. K., Dulović, M., Zogović, N., Isaković, A. M., Grgurić-Sipka, S. R., Bumbaširević, V. Z., Sabo, T. J., Trajković, V. S.,& Marković, I. D.. (2012). Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology, 25(4).
https://hdl.handle.net/21.15107/rcub_ibiss_1196

Misirlić-Dencić ST, Poljarević JM, Vilimanović U, Bogdanović AD, Isaković AJ, Kravić-Stevović TK, Dulović M, Zogović N, Isaković AM, Grgurić-Sipka SR, Bumbaširević VZ, Sabo TJ, Trajković VS, Marković ID. Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology. 2012;25(4):null-939.
https://hdl.handle.net/21.15107/rcub_ibiss_1196 .

Misirlić-Dencić, Sonja T, Poljarević, Jelena M, Vilimanović, Uros, Bogdanović, Andrija D, Isaković, Aleksandra J, Kravić-Stevović, Tamara K, Dulović, Marija, Zogović, Nevena, Isaković, Anđelka M, Grgurić-Sipka, Sanja R, Bumbaširević, Vladimir Z, Sabo, Tibor J, Trajković, Vladimir S, Marković, Ivanka D, "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells" in Chemical Research in Toxicology, 25, no. 4 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1196 .

TY  - JOUR
AU  - Stevanović, Darko M
AU  - Starčević, Vesna P.
AU  - Vilimanović, Uros
AU  - Nesić, Dejan M
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Savić, Emina
AU  - Popadić, Dusan M
AU  - Sudar, Emina M
AU  - Micić, Dragan D
AU  - Sumarac-Dumanović, Mirjana S
AU  - Trajković, Vladimir S
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1238
AB  - We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1 beta, IFN-gamma) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1 beta, IL-6, IFN-gamma, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-beta remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 mu g/day) for five consecutive days significantly reduced TNF, IL-1 beta and IFN-gamma levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of 1FN-gamma, IL-17,1L-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. (C) 2011 Elsevier Inc. All rights reserved.
T2  - Brain Behavior and Immunity
T1  - Immunomodulatory actions of central ghrelin in diet-induced energy imbalance
IS  - 1
VL  - 26
EP  - 158
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1238
ER  - 

@article{
author = "Stevanović, Darko M and Starčević, Vesna P. and Vilimanović, Uros and Nesić, Dejan M and Vučićević, Ljubica and Misirkić Marjanović, Maja and Janjetović, Kristina and Savić, Emina and Popadić, Dusan M and Sudar, Emina M and Micić, Dragan D and Sumarac-Dumanović, Mirjana S and Trajković, Vladimir S",
year = "2012",
abstract = "We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1 beta, IFN-gamma) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1 beta, IL-6, IFN-gamma, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-beta remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 mu g/day) for five consecutive days significantly reduced TNF, IL-1 beta and IFN-gamma levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of 1FN-gamma, IL-17,1L-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. (C) 2011 Elsevier Inc. All rights reserved.",
journal = "Brain Behavior and Immunity",
title = "Immunomodulatory actions of central ghrelin in diet-induced energy imbalance",
number = "1",
volume = "26",
pages = "158",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1238"
}

Stevanović, D. M., Starčević, V. P., Vilimanović, U., Nesić, D. M., Vučićević, L., Misirkić Marjanović, M., Janjetović, K., Savić, E., Popadić, D. M., Sudar, E. M., Micić, D. D., Sumarac-Dumanović, M. S.,& Trajković, V. S.. (2012). Immunomodulatory actions of central ghrelin in diet-induced energy imbalance. in Brain Behavior and Immunity, 26(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1238

Stevanović DM, Starčević VP, Vilimanović U, Nesić DM, Vučićević L, Misirkić Marjanović M, Janjetović K, Savić E, Popadić DM, Sudar EM, Micić DD, Sumarac-Dumanović MS, Trajković VS. Immunomodulatory actions of central ghrelin in diet-induced energy imbalance. in Brain Behavior and Immunity. 2012;26(1):null-158.
https://hdl.handle.net/21.15107/rcub_ibiss_1238 .

Stevanović, Darko M, Starčević, Vesna P., Vilimanović, Uros, Nesić, Dejan M, Vučićević, Ljubica, Misirkić Marjanović, Maja, Janjetović, Kristina, Savić, Emina, Popadić, Dusan M, Sudar, Emina M, Micić, Dragan D, Sumarac-Dumanović, Mirjana S, Trajković, Vladimir S, "Immunomodulatory actions of central ghrelin in diet-induced energy imbalance" in Brain Behavior and Immunity, 26, no. 1 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1238 .

TY  - JOUR
AU  - Stevanović, Darko M
AU  - Janjetović, Kristina
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Sumarac-Dumanović, Mirjana S
AU  - Micić, Dragan D
AU  - Starčević, Vesna P.
AU  - Trajković, Vladimir S
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1226
AB  - Background/Aims: The antihyperglycaemic drug metformin reduces food consumption through mechanisms that are not fully elucidated. The present study investigated the effects of intracerebroventricular administration of metformin on food intake and hypothalamic appetite-regulating signalling pathways induced by the orexigenic peptide ghrelin. Methods: Rats were injected intracerebroventricularly with ghrelin (5 mu g), metformin (50, 100 or 200 mu g), 5-amino-imidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR, 25 mu g) and L-Ieucine (1 mu g) in different combinations. Food intake was monitored during the next 4 h. Hypothalamic activation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), regulatory-associated protein of mTOR (Raptor), mammalian target of rapamycin (mTOR) and p70 S6 kinase 1 (S6K) after 1 h of treatment was analysed by immunoblotting. Results: Metformin suppressed the increase in food consumption induced by intracerebroventricular ghrelin in a dose-dependent manner. Ghrelin increased phosphorylation of hypothalamic AMPK and its targets ACC and Raptor, which was associated with the reduced phosphorylation of mTOR. The mTOR substrate, 56K, was activated by intracerebroventricular ghrelin despite the inhibition of mTOR. Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting 56K phosphorylation. Metformin also reduced food consumption induced by the AMPK activator AICAR while the ghrelin-triggered food intake was inhibited by the mTOR activator L-leucine. Conclusion: Metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus. Copyright (c) 2012 S. Karger AG, Basel
T2  - Neuroendocrinology
T1  - Intracerebroventricular Administration of Metformin Inhibits Ghrelin-Induced Hypothalamic AMP-Kinase Signalling and Food Intake
IS  - 1
VL  - 96
EP  - 31
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1226
ER  - 

@article{
author = "Stevanović, Darko M and Janjetović, Kristina and Misirkić Marjanović, Maja and Vučićević, Ljubica and Sumarac-Dumanović, Mirjana S and Micić, Dragan D and Starčević, Vesna P. and Trajković, Vladimir S",
year = "2012",
abstract = "Background/Aims: The antihyperglycaemic drug metformin reduces food consumption through mechanisms that are not fully elucidated. The present study investigated the effects of intracerebroventricular administration of metformin on food intake and hypothalamic appetite-regulating signalling pathways induced by the orexigenic peptide ghrelin. Methods: Rats were injected intracerebroventricularly with ghrelin (5 mu g), metformin (50, 100 or 200 mu g), 5-amino-imidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR, 25 mu g) and L-Ieucine (1 mu g) in different combinations. Food intake was monitored during the next 4 h. Hypothalamic activation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), regulatory-associated protein of mTOR (Raptor), mammalian target of rapamycin (mTOR) and p70 S6 kinase 1 (S6K) after 1 h of treatment was analysed by immunoblotting. Results: Metformin suppressed the increase in food consumption induced by intracerebroventricular ghrelin in a dose-dependent manner. Ghrelin increased phosphorylation of hypothalamic AMPK and its targets ACC and Raptor, which was associated with the reduced phosphorylation of mTOR. The mTOR substrate, 56K, was activated by intracerebroventricular ghrelin despite the inhibition of mTOR. Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting 56K phosphorylation. Metformin also reduced food consumption induced by the AMPK activator AICAR while the ghrelin-triggered food intake was inhibited by the mTOR activator L-leucine. Conclusion: Metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus. Copyright (c) 2012 S. Karger AG, Basel",
journal = "Neuroendocrinology",
title = "Intracerebroventricular Administration of Metformin Inhibits Ghrelin-Induced Hypothalamic AMP-Kinase Signalling and Food Intake",
number = "1",
volume = "96",
pages = "31",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1226"
}

Stevanović, D. M., Janjetović, K., Misirkić Marjanović, M., Vučićević, L., Sumarac-Dumanović, M. S., Micić, D. D., Starčević, V. P.,& Trajković, V. S.. (2012). Intracerebroventricular Administration of Metformin Inhibits Ghrelin-Induced Hypothalamic AMP-Kinase Signalling and Food Intake. in Neuroendocrinology, 96(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1226

Stevanović DM, Janjetović K, Misirkić Marjanović M, Vučićević L, Sumarac-Dumanović MS, Micić DD, Starčević VP, Trajković VS. Intracerebroventricular Administration of Metformin Inhibits Ghrelin-Induced Hypothalamic AMP-Kinase Signalling and Food Intake. in Neuroendocrinology. 2012;96(1):null-31.
https://hdl.handle.net/21.15107/rcub_ibiss_1226 .

Stevanović, Darko M, Janjetović, Kristina, Misirkić Marjanović, Maja, Vučićević, Ljubica, Sumarac-Dumanović, Mirjana S, Micić, Dragan D, Starčević, Vesna P., Trajković, Vladimir S, "Intracerebroventricular Administration of Metformin Inhibits Ghrelin-Induced Hypothalamic AMP-Kinase Signalling and Food Intake" in Neuroendocrinology, 96, no. 1 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1226 .

TY  - JOUR
AU  - Radović, Julijana M
AU  - Maksimović-Ivanić, Danijela
AU  - Timotijević, Gordana S
AU  - Popadić, S
AU  - Ramić, Zorica D.
AU  - Trajković, Vladimir S
AU  - Miljković, Đorđe
AU  - Stošić-Grujičić, Stanislava
AU  - Mijatović, Sanja
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1135
AB  - Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H2O2 production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - Food and Chemical Toxicology
T1  - Cell-type dependent response of melanoma cells to aloe emodin
IS  - 9
VL  - 50
SP  - 911
EP  - 3189
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1135
ER  - 

@article{
author = "Radović, Julijana M and Maksimović-Ivanić, Danijela and Timotijević, Gordana S and Popadić, S and Ramić, Zorica D. and Trajković, Vladimir S and Miljković, Đorđe and Stošić-Grujičić, Stanislava and Mijatović, Sanja",
year = "2012",
abstract = "Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H2O2 production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "Food and Chemical Toxicology",
title = "Cell-type dependent response of melanoma cells to aloe emodin",
number = "9",
volume = "50",
pages = "911-3189",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1135"
}

Radović, J. M., Maksimović-Ivanić, D., Timotijević, G. S., Popadić, S., Ramić, Z. D., Trajković, V. S., Miljković, Đ., Stošić-Grujičić, S.,& Mijatović, S.. (2012). Cell-type dependent response of melanoma cells to aloe emodin. in Food and Chemical Toxicology, 50(9), 911-3189.
https://hdl.handle.net/21.15107/rcub_ibiss_1135

Radović JM, Maksimović-Ivanić D, Timotijević GS, Popadić S, Ramić ZD, Trajković VS, Miljković Đ, Stošić-Grujičić S, Mijatović S. Cell-type dependent response of melanoma cells to aloe emodin. in Food and Chemical Toxicology. 2012;50(9):911-3189.
https://hdl.handle.net/21.15107/rcub_ibiss_1135 .

Radović, Julijana M, Maksimović-Ivanić, Danijela, Timotijević, Gordana S, Popadić, S, Ramić, Zorica D., Trajković, Vladimir S, Miljković, Đorđe, Stošić-Grujičić, Stanislava, Mijatović, Sanja, "Cell-type dependent response of melanoma cells to aloe emodin" in Food and Chemical Toxicology, 50, no. 9 (2012):911-3189,
https://hdl.handle.net/21.15107/rcub_ibiss_1135 .

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Mirkov, Ivana
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Đorđe
AU  - Sabo, Tibor J
AU  - Trajković, Vladimir S
AU  - Kaluđerović, Goran N.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1088
AB  - Tetrachlorido(O,O'-dibutyl-ethylenediamine-N,N'-di-3-propionate)-platinum(IV) complex, [PtCl4(n-Bu(2)eddp)], was previously found to be effective against fibrosarcoma and glioma cell lines. Here we presented that [PtCl4(n-Bu(2)eddp)] strongly reduced the growth of B16 melanoma cells in vitro. Inhibition of cell viability was accompanied with induction of both necrotic and apoptotic cell death. In addition, [PtCl4(n-Bu(2)eddp)] concealed the expansion of tumors induced in syngeneic C57BI/6 mice without visible signs of nephrotoxicity.
T2  - Metallomics
T1  - Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations
IS  - 11
VL  - 4
SP  - 222
EP  - 1159
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1088
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Mirkov, Ivana and Stošić-Grujičić, Stanislava and Miljković, Đorđe and Sabo, Tibor J and Trajković, Vladimir S and Kaluđerović, Goran N.",
year = "2012",
abstract = "Tetrachlorido(O,O'-dibutyl-ethylenediamine-N,N'-di-3-propionate)-platinum(IV) complex, [PtCl4(n-Bu(2)eddp)], was previously found to be effective against fibrosarcoma and glioma cell lines. Here we presented that [PtCl4(n-Bu(2)eddp)] strongly reduced the growth of B16 melanoma cells in vitro. Inhibition of cell viability was accompanied with induction of both necrotic and apoptotic cell death. In addition, [PtCl4(n-Bu(2)eddp)] concealed the expansion of tumors induced in syngeneic C57BI/6 mice without visible signs of nephrotoxicity.",
journal = "Metallomics",
title = "Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations",
number = "11",
volume = "4",
pages = "222-1159",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1088"
}

Maksimović-Ivanić, D., Mijatović, S., Mirkov, I., Stošić-Grujičić, S., Miljković, Đ., Sabo, T. J., Trajković, V. S.,& Kaluđerović, G. N.. (2012). Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations. in Metallomics, 4(11), 222-1159.
https://hdl.handle.net/21.15107/rcub_ibiss_1088

Maksimović-Ivanić D, Mijatović S, Mirkov I, Stošić-Grujičić S, Miljković Đ, Sabo TJ, Trajković VS, Kaluđerović GN. Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations. in Metallomics. 2012;4(11):222-1159.
https://hdl.handle.net/21.15107/rcub_ibiss_1088 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Mirkov, Ivana, Stošić-Grujičić, Stanislava, Miljković, Đorđe, Sabo, Tibor J, Trajković, Vladimir S, Kaluđerović, Goran N., "Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations" in Metallomics, 4, no. 11 (2012):222-1159,
https://hdl.handle.net/21.15107/rcub_ibiss_1088 .

TY  - JOUR
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vilimanović, Uros
AU  - Sudar, Emina M
AU  - Isenović, Esma R
AU  - Prica, Marko
AU  - Harhaji-Trajković, Ljubica
AU  - Kravić-Stevović, Tamara K
AU  - Bumbaširević, Vladimir Z
AU  - Trajković, Vladimir S
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1321
AB  - In the present study, we report that compound C, an inhibitor of a key intracellular energy sensor AMP-activated protein kinase (AMPK), can induce autophagy in cancer cells. The induction of autophagy in U251 human glioma cell line was demonstrated by acridine orange staining of intracellular acidic vesicles, Beclin 1 induction, p62 decrease and conversion of LC3-I to autophagosome-associated LC3-II in the presence of proteolysis inhibitors. The presence of autophagosome-like vesicles was confirmed by transmission electron microscopy. Compound C-mediated inhibition of AMPK and raptor in U251 cells was associated with paradoxical decrease in phosphorylation of AMPK/raptor-repressed mTOR, a major negative regulator of autophagy, and its downstream target p70S6K. The phosphorylation of an mTOR activator Akt and the PI3K-activating kinase Src was also impaired in compound C-treated cells. The siRNA-mediated AMPK silencing did not reduce the activity of the Akt/mTOR/p70S6K pathway and AMPK activators metformin and AICAR failed to block compound C-induced autophagy. Autophagy inhibitors bafilomycin and chloroquine significantly increased the cytotoxicity of compound C towards U251 cells, as confirmed by increase in lactate dehydrogenase release, DNA fragmentation and caspase-3 activation. Similar effects of compound C were also observed in C6 rat glioma, L929 mouse fibrosarcoma and B16 mouse melanoma cell lines. Since compound C has previously been reported to suppress AMPK-dependent autophagy in different cell types, our findings suggest that the effects of compound C on autophagy might be dose-, cell type- and/or context-dependent. By demonstrating the ability of compound C to induce autophagic response in cancer cells via AMPK inhibition-independent downregulation of Akt/mTOR pathway, our results warrant caution when using compound C to inhibit AMPK-dependent cellular responses, but also support further exploration of compound C and related molecules as potential anticancer agents.
T2  - Autophagy
T1  - Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway
IS  - 1
VL  - 7
DO  - 10.4161/auto.7.1.13883
EP  - 50
ER  - 

@article{
author = "Vučićević, Ljubica and Misirkić Marjanović, Maja and Janjetović, Kristina and Vilimanović, Uros and Sudar, Emina M and Isenović, Esma R and Prica, Marko and Harhaji-Trajković, Ljubica and Kravić-Stevović, Tamara K and Bumbaširević, Vladimir Z and Trajković, Vladimir S",
year = "2011",
abstract = "In the present study, we report that compound C, an inhibitor of a key intracellular energy sensor AMP-activated protein kinase (AMPK), can induce autophagy in cancer cells. The induction of autophagy in U251 human glioma cell line was demonstrated by acridine orange staining of intracellular acidic vesicles, Beclin 1 induction, p62 decrease and conversion of LC3-I to autophagosome-associated LC3-II in the presence of proteolysis inhibitors. The presence of autophagosome-like vesicles was confirmed by transmission electron microscopy. Compound C-mediated inhibition of AMPK and raptor in U251 cells was associated with paradoxical decrease in phosphorylation of AMPK/raptor-repressed mTOR, a major negative regulator of autophagy, and its downstream target p70S6K. The phosphorylation of an mTOR activator Akt and the PI3K-activating kinase Src was also impaired in compound C-treated cells. The siRNA-mediated AMPK silencing did not reduce the activity of the Akt/mTOR/p70S6K pathway and AMPK activators metformin and AICAR failed to block compound C-induced autophagy. Autophagy inhibitors bafilomycin and chloroquine significantly increased the cytotoxicity of compound C towards U251 cells, as confirmed by increase in lactate dehydrogenase release, DNA fragmentation and caspase-3 activation. Similar effects of compound C were also observed in C6 rat glioma, L929 mouse fibrosarcoma and B16 mouse melanoma cell lines. Since compound C has previously been reported to suppress AMPK-dependent autophagy in different cell types, our findings suggest that the effects of compound C on autophagy might be dose-, cell type- and/or context-dependent. By demonstrating the ability of compound C to induce autophagic response in cancer cells via AMPK inhibition-independent downregulation of Akt/mTOR pathway, our results warrant caution when using compound C to inhibit AMPK-dependent cellular responses, but also support further exploration of compound C and related molecules as potential anticancer agents.",
journal = "Autophagy",
title = "Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway",
number = "1",
volume = "7",
doi = "10.4161/auto.7.1.13883",
pages = "50"
}

Vučićević, L., Misirkić Marjanović, M., Janjetović, K., Vilimanović, U., Sudar, E. M., Isenović, E. R., Prica, M., Harhaji-Trajković, L., Kravić-Stevović, T. K., Bumbaširević, V. Z.,& Trajković, V. S.. (2011). Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. in Autophagy, 7(1).
https://doi.org/10.4161/auto.7.1.13883

Vučićević L, Misirkić Marjanović M, Janjetović K, Vilimanović U, Sudar EM, Isenović ER, Prica M, Harhaji-Trajković L, Kravić-Stevović TK, Bumbaširević VZ, Trajković VS. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. in Autophagy. 2011;7(1):null-50.
doi:10.4161/auto.7.1.13883 .

Vučićević, Ljubica, Misirkić Marjanović, Maja, Janjetović, Kristina, Vilimanović, Uros, Sudar, Emina M, Isenović, Esma R, Prica, Marko, Harhaji-Trajković, Ljubica, Kravić-Stevović, Tamara K, Bumbaširević, Vladimir Z, Trajković, Vladimir S, "Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway" in Autophagy, 7, no. 1 (2011),
https://doi.org/10.4161/auto.7.1.13883 . .

TY  - JOUR
AU  - Sudar, Emina M
AU  - Dobutović, Branislava D
AU  - Soskić, Sanja S
AU  - Mandušić, Vesna
AU  - Zakula, Zorica
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Janjetović, Kristina
AU  - Trajković, Vladimir S
AU  - Mikhailidis, Dimitri P
AU  - Isenović, Esma R
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1121
AB  - The purpose of this study was to examine the effects of ghrelin on protein kinase B (Akt) and mitogen-activated protein kinase p42/44 (ERK1/2) activation as well as ghrelin effects on inducible nitric oxide (NO) synthase (iNOS; for gene Nos2) activity/expression in rat hearts. Male Wistar rats were treated with ghrelin (0.3 nmol/5 mu l) or an equal volume of phosphate-buffered saline, injected every 24 h into the lateral cerebral ventricle for 5 days and 2 h after the last treatment the animals were sacrificed. Serum NO, l-arginine (l-Arg), and arginase activity were measured spectrophotometrically. For phosphorylation of Akt, ERK1/2, and iNOS protein expression, Western blot method was used. The expression of Nos2 mRNA was measured by the quantitative real-time polymerase chain reaction (qRT-PCR). Treatment with ghrelin significantly increased NO production in serum by 1.4-fold compared with control. The concentration of l-Arg was significantly higher in ghrelin-treated rats than in control while arginase activity was significantly lower in ghrelin-treated than in control hearts. Ghrelin treatment increased phosphorylation of Akt by 1.9-fold and ERK1/2 by 1.6-fold and increased iNOS expression by 2.5-fold compared with control. In addition, ghrelin treatment increased Nos2 gene expression by 2.2-fold as determined by qRT-PCR. These results indicate that ghrelin regulation of iNOS expression/activity is mediated via Akt/ERK1/2 signaling pathway. These results may be relevant to understanding molecular mechanisms underlying direct cardiovascular actions of ghrelin.
T2  - Journal of Physiology and Biochemistry
T1  - Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats
IS  - 2
VL  - 67
SP  - 483
EP  - 204
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1121
ER  - 

@article{
author = "Sudar, Emina M and Dobutović, Branislava D and Soskić, Sanja S and Mandušić, Vesna and Zakula, Zorica and Misirkić Marjanović, Maja and Vučićević, Ljubica and Janjetović, Kristina and Trajković, Vladimir S and Mikhailidis, Dimitri P and Isenović, Esma R",
year = "2011",
abstract = "The purpose of this study was to examine the effects of ghrelin on protein kinase B (Akt) and mitogen-activated protein kinase p42/44 (ERK1/2) activation as well as ghrelin effects on inducible nitric oxide (NO) synthase (iNOS; for gene Nos2) activity/expression in rat hearts. Male Wistar rats were treated with ghrelin (0.3 nmol/5 mu l) or an equal volume of phosphate-buffered saline, injected every 24 h into the lateral cerebral ventricle for 5 days and 2 h after the last treatment the animals were sacrificed. Serum NO, l-arginine (l-Arg), and arginase activity were measured spectrophotometrically. For phosphorylation of Akt, ERK1/2, and iNOS protein expression, Western blot method was used. The expression of Nos2 mRNA was measured by the quantitative real-time polymerase chain reaction (qRT-PCR). Treatment with ghrelin significantly increased NO production in serum by 1.4-fold compared with control. The concentration of l-Arg was significantly higher in ghrelin-treated rats than in control while arginase activity was significantly lower in ghrelin-treated than in control hearts. Ghrelin treatment increased phosphorylation of Akt by 1.9-fold and ERK1/2 by 1.6-fold and increased iNOS expression by 2.5-fold compared with control. In addition, ghrelin treatment increased Nos2 gene expression by 2.2-fold as determined by qRT-PCR. These results indicate that ghrelin regulation of iNOS expression/activity is mediated via Akt/ERK1/2 signaling pathway. These results may be relevant to understanding molecular mechanisms underlying direct cardiovascular actions of ghrelin.",
journal = "Journal of Physiology and Biochemistry",
title = "Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats",
number = "2",
volume = "67",
pages = "483-204",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1121"
}

Sudar, E. M., Dobutović, B. D., Soskić, S. S., Mandušić, V., Zakula, Z., Misirkić Marjanović, M., Vučićević, L., Janjetović, K., Trajković, V. S., Mikhailidis, D. P.,& Isenović, E. R.. (2011). Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats. in Journal of Physiology and Biochemistry, 67(2), 483-204.
https://hdl.handle.net/21.15107/rcub_ibiss_1121

Sudar EM, Dobutović BD, Soskić SS, Mandušić V, Zakula Z, Misirkić Marjanović M, Vučićević L, Janjetović K, Trajković VS, Mikhailidis DP, Isenović ER. Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats. in Journal of Physiology and Biochemistry. 2011;67(2):483-204.
https://hdl.handle.net/21.15107/rcub_ibiss_1121 .

Sudar, Emina M, Dobutović, Branislava D, Soskić, Sanja S, Mandušić, Vesna, Zakula, Zorica, Misirkić Marjanović, Maja, Vučićević, Ljubica, Janjetović, Kristina, Trajković, Vladimir S, Mikhailidis, Dimitri P, Isenović, Esma R, "Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats" in Journal of Physiology and Biochemistry, 67, no. 2 (2011):483-204,
https://hdl.handle.net/21.15107/rcub_ibiss_1121 .

TY  - JOUR
AU  - Trpković, Andreja
AU  - Todorović-Marković, Biljana M
AU  - Kleut, Duska N
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Pantović, Aleksandar C
AU  - Jovanović, Svetlana P
AU  - Dramicanin, Miroslav D
AU  - Marković, Zoran J
AU  - Trajković, Vladimir S
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1140
AB  - The present study investigated the hemolytic properties of fullerene (C-60) nanoparticles prepared by solvent exchange using tetrahydrofuran (nC(60)THF), or by mechanochemically assisted complexation with macrocyclic oligosaccharide gamma-cyclodextrin (nC(60)CDX) or the copolymer ethylene vinyl acetate-ethylene vinyl versatate (nC(60)EVA-EVV). The spectrophotometrical analysis of hemoglobin release revealed that only nC(60)THF, but not nC(60)CDX or nC(60)EVA-EVV, was able to cause lysis of human erythrocytes in a dose-and time-dependent manner. Atomic force microscopy revealed that nC(60)THF-mediated hemolysis was preceded by erythrocyte shrinkage and increase in cell surface roughness. A flow cytometric analysis confirmed a decrease in erythrocyte size and demonstrated a significant increase in reactive oxygen species production in red blood cells exposed to nC(60)THF. The nC(60)THF-triggered hemolytic activity was efficiently reduced by the antioxidants N-acetylcysteine and butylated hydroxyanisole, as well as by serum albumin, the most abundant protein in human blood plasma. These data indicate that nC(60)THF can cause serum albumin-preventable hemolysis through oxidative stress-mediated damage of the erythrocyte membrane.
T2  - Nanotechnology
T1  - Oxidative stress-mediated hemolytic activity of solvent exchange-prepared fullerene (C-60) nanoparticles
IS  - 37
VL  - 21
SP  - 601
EP  - na
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1140
ER  - 

@article{
author = "Trpković, Andreja and Todorović-Marković, Biljana M and Kleut, Duska N and Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Pantović, Aleksandar C and Jovanović, Svetlana P and Dramicanin, Miroslav D and Marković, Zoran J and Trajković, Vladimir S",
year = "2010",
abstract = "The present study investigated the hemolytic properties of fullerene (C-60) nanoparticles prepared by solvent exchange using tetrahydrofuran (nC(60)THF), or by mechanochemically assisted complexation with macrocyclic oligosaccharide gamma-cyclodextrin (nC(60)CDX) or the copolymer ethylene vinyl acetate-ethylene vinyl versatate (nC(60)EVA-EVV). The spectrophotometrical analysis of hemoglobin release revealed that only nC(60)THF, but not nC(60)CDX or nC(60)EVA-EVV, was able to cause lysis of human erythrocytes in a dose-and time-dependent manner. Atomic force microscopy revealed that nC(60)THF-mediated hemolysis was preceded by erythrocyte shrinkage and increase in cell surface roughness. A flow cytometric analysis confirmed a decrease in erythrocyte size and demonstrated a significant increase in reactive oxygen species production in red blood cells exposed to nC(60)THF. The nC(60)THF-triggered hemolytic activity was efficiently reduced by the antioxidants N-acetylcysteine and butylated hydroxyanisole, as well as by serum albumin, the most abundant protein in human blood plasma. These data indicate that nC(60)THF can cause serum albumin-preventable hemolysis through oxidative stress-mediated damage of the erythrocyte membrane.",
journal = "Nanotechnology",
title = "Oxidative stress-mediated hemolytic activity of solvent exchange-prepared fullerene (C-60) nanoparticles",
number = "37",
volume = "21",
pages = "601-na",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1140"
}

Trpković, A., Todorović-Marković, B. M., Kleut, D. N., Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Pantović, A. C., Jovanović, S. P., Dramicanin, M. D., Marković, Z. J.,& Trajković, V. S.. (2010). Oxidative stress-mediated hemolytic activity of solvent exchange-prepared fullerene (C-60) nanoparticles. in Nanotechnology, 21(37), 601-na.
https://hdl.handle.net/21.15107/rcub_ibiss_1140

Trpković A, Todorović-Marković BM, Kleut DN, Misirkić Marjanović M, Janjetović K, Vučićević L, Pantović AC, Jovanović SP, Dramicanin MD, Marković ZJ, Trajković VS. Oxidative stress-mediated hemolytic activity of solvent exchange-prepared fullerene (C-60) nanoparticles. in Nanotechnology. 2010;21(37):601-na.
https://hdl.handle.net/21.15107/rcub_ibiss_1140 .

Trpković, Andreja, Todorović-Marković, Biljana M, Kleut, Duska N, Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Pantović, Aleksandar C, Jovanović, Svetlana P, Dramicanin, Miroslav D, Marković, Zoran J, Trajković, Vladimir S, "Oxidative stress-mediated hemolytic activity of solvent exchange-prepared fullerene (C-60) nanoparticles" in Nanotechnology, 21, no. 37 (2010):601-na,
https://hdl.handle.net/21.15107/rcub_ibiss_1140 .

TY  - JOUR
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Harhaji-Trajković, Ljubica
AU  - Prica, Marko
AU  - Stevanović, Darko M
AU  - Isenović, Esma R
AU  - Sudar, Emina M
AU  - Sumarac-Dumanović, Mirjana S
AU  - Micić, Dragan D
AU  - Trajković, Vladimir S
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1446
AB  - We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G(2)/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells. (c) 2009 Elsevier Inc. All rights reserved.
T2  - Biochemical Pharmacology
T1  - AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C
IS  - 11
VL  - 77
EP  - 1693
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1446
ER  - 

@article{
author = "Vučićević, Ljubica and Misirkić Marjanović, Maja and Janjetović, Kristina and Harhaji-Trajković, Ljubica and Prica, Marko and Stevanović, Darko M and Isenović, Esma R and Sudar, Emina M and Sumarac-Dumanović, Mirjana S and Micić, Dragan D and Trajković, Vladimir S",
year = "2009",
abstract = "We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G(2)/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells. (c) 2009 Elsevier Inc. All rights reserved.",
journal = "Biochemical Pharmacology",
title = "AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C",
number = "11",
volume = "77",
pages = "1693",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1446"
}

Vučićević, L., Misirkić Marjanović, M., Janjetović, K., Harhaji-Trajković, L., Prica, M., Stevanović, D. M., Isenović, E. R., Sudar, E. M., Sumarac-Dumanović, M. S., Micić, D. D.,& Trajković, V. S.. (2009). AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. in Biochemical Pharmacology, 77(11).
https://hdl.handle.net/21.15107/rcub_ibiss_1446

Vučićević L, Misirkić Marjanović M, Janjetović K, Harhaji-Trajković L, Prica M, Stevanović DM, Isenović ER, Sudar EM, Sumarac-Dumanović MS, Micić DD, Trajković VS. AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. in Biochemical Pharmacology. 2009;77(11):null-1693.
https://hdl.handle.net/21.15107/rcub_ibiss_1446 .

Vučićević, Ljubica, Misirkić Marjanović, Maja, Janjetović, Kristina, Harhaji-Trajković, Ljubica, Prica, Marko, Stevanović, Darko M, Isenović, Esma R, Sudar, Emina M, Sumarac-Dumanović, Mirjana S, Micić, Dragan D, Trajković, Vladimir S, "AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C" in Biochemical Pharmacology, 77, no. 11 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1446 .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Todorović-Marković, Biljana M
AU  - Vučićević, Ljubica
AU  - Janjetović, Kristina
AU  - Jokanović, Vukoman R
AU  - Dramicanin, Miroslav D
AU  - Marković, Zoran M
AU  - Trajković, Vladimir S
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1456
AB  - The influence of fullerene (C-60) nanoparticles on the cytotoxicity of a highly reactive free radical nitric oxide (NO) was investigated. Fullerene nanoparticles were prepared by mechanochemically assisted complexation with anionic surfactant sodium dodecyl sulfate, macrocyclic oligosaccharide gamma-cyclodextrin or the copolymer ethylene vinyl acetate-ethylene vinyl versatate. C-60 nanoparticles were characterized by UV-vis and atomic force microscopy. While readily internalized by mouse L929 fibroblasts, C-60 nanoparticles were not cytotoxic. Moreover, they partially protected L929 cells from the cytotoxic effect of NO-releasing compounds sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione (GSNO) and 3-morpholino-sydnonimine (SIN-1). C-60 nanoparticles reduced SNP-induced apoptotic cell death by preventing mitochondrial depolarization, caspase activation, cell membrane phosphatidylserine exposure and DNA fragmentation. The protective action of C-60 nanoparticles was not exerted via direct interaction with NO, but through neutralization of mitochondria-produced superoxide radical in NO-treated cells, as demonstrated by using different redox-sensitive reporter fluorochromes. These data suggest that C-60 complexes with appropriate host molecules might be plausible candidates for preventing NO-mediated cell injury in inflammatory/autoimmune disorders. (C) 2009 Elsevier Ltd. All rights reserved.
T2  - Biomaterials
T1  - The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C-60) nanoparticles
IS  - 12
VL  - 30
EP  - 2328
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1456
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Todorović-Marković, Biljana M and Vučićević, Ljubica and Janjetović, Kristina and Jokanović, Vukoman R and Dramicanin, Miroslav D and Marković, Zoran M and Trajković, Vladimir S",
year = "2009",
abstract = "The influence of fullerene (C-60) nanoparticles on the cytotoxicity of a highly reactive free radical nitric oxide (NO) was investigated. Fullerene nanoparticles were prepared by mechanochemically assisted complexation with anionic surfactant sodium dodecyl sulfate, macrocyclic oligosaccharide gamma-cyclodextrin or the copolymer ethylene vinyl acetate-ethylene vinyl versatate. C-60 nanoparticles were characterized by UV-vis and atomic force microscopy. While readily internalized by mouse L929 fibroblasts, C-60 nanoparticles were not cytotoxic. Moreover, they partially protected L929 cells from the cytotoxic effect of NO-releasing compounds sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione (GSNO) and 3-morpholino-sydnonimine (SIN-1). C-60 nanoparticles reduced SNP-induced apoptotic cell death by preventing mitochondrial depolarization, caspase activation, cell membrane phosphatidylserine exposure and DNA fragmentation. The protective action of C-60 nanoparticles was not exerted via direct interaction with NO, but through neutralization of mitochondria-produced superoxide radical in NO-treated cells, as demonstrated by using different redox-sensitive reporter fluorochromes. These data suggest that C-60 complexes with appropriate host molecules might be plausible candidates for preventing NO-mediated cell injury in inflammatory/autoimmune disorders. (C) 2009 Elsevier Ltd. All rights reserved.",
journal = "Biomaterials",
title = "The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C-60) nanoparticles",
number = "12",
volume = "30",
pages = "2328",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1456"
}

Misirkić Marjanović, M., Todorović-Marković, B. M., Vučićević, L., Janjetović, K., Jokanović, V. R., Dramicanin, M. D., Marković, Z. M.,& Trajković, V. S.. (2009). The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C-60) nanoparticles. in Biomaterials, 30(12).
https://hdl.handle.net/21.15107/rcub_ibiss_1456

Misirkić Marjanović M, Todorović-Marković BM, Vučićević L, Janjetović K, Jokanović VR, Dramicanin MD, Marković ZM, Trajković VS. The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C-60) nanoparticles. in Biomaterials. 2009;30(12):null-2328.
https://hdl.handle.net/21.15107/rcub_ibiss_1456 .

Misirkić Marjanović, Maja, Todorović-Marković, Biljana M, Vučićević, Ljubica, Janjetović, Kristina, Jokanović, Vukoman R, Dramicanin, Miroslav D, Marković, Zoran M, Trajković, Vladimir S, "The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C-60) nanoparticles" in Biomaterials, 30, no. 12 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1456 .

TY  - JOUR
AU  - Isaković, Aleksandra J
AU  - Janković, Teodora
AU  - Harhaji-Trajković, Ljubica
AU  - Kostić-Rajačić, Slađana V.
AU  - Nikolić, Zoran M
AU  - Vajs, Vlatka E
AU  - Trajković, Vladimir S
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1530
AB  - The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G(2)/M and G(0)/G(1) phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G(2)/M cell block and apoptotic cell death in glioma cells. (C) 2008 Elsevier Ltd. All rights reserved.
T2  - Bioorganic & Medicinal Chemistry
T1  - Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements
IS  - 10
VL  - 16
EP  - 5694
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1530
ER  - 

@article{
author = "Isaković, Aleksandra J and Janković, Teodora and Harhaji-Trajković, Ljubica and Kostić-Rajačić, Slađana V. and Nikolić, Zoran M and Vajs, Vlatka E and Trajković, Vladimir S",
year = "2008",
abstract = "The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G(2)/M and G(0)/G(1) phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G(2)/M cell block and apoptotic cell death in glioma cells. (C) 2008 Elsevier Ltd. All rights reserved.",
journal = "Bioorganic & Medicinal Chemistry",
title = "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements",
number = "10",
volume = "16",
pages = "5694",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1530"
}

Isaković, A. J., Janković, T., Harhaji-Trajković, L., Kostić-Rajačić, S. V., Nikolić, Z. M., Vajs, V. E.,& Trajković, V. S.. (2008). Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic & Medicinal Chemistry, 16(10).
https://hdl.handle.net/21.15107/rcub_ibiss_1530

Isaković AJ, Janković T, Harhaji-Trajković L, Kostić-Rajačić SV, Nikolić ZM, Vajs VE, Trajković VS. Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic & Medicinal Chemistry. 2008;16(10):null-5694.
https://hdl.handle.net/21.15107/rcub_ibiss_1530 .

Isaković, Aleksandra J, Janković, Teodora, Harhaji-Trajković, Ljubica, Kostić-Rajačić, Slađana V., Nikolić, Zoran M, Vajs, Vlatka E, Trajković, Vladimir S, "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements" in Bioorganic & Medicinal Chemistry, 16, no. 10 (2008),
https://hdl.handle.net/21.15107/rcub_ibiss_1530 .

TY  - JOUR
AU  - Zogović, Nevena
AU  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Harhaji-Trajković, Ljubica
AU  - Miljković, Đorđe
AU  - Trajković, Vladimir
PY  - 2005
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6013
AB  - The role of iron in 6-hydroxydopamine (6-OHDA) toxicity towards astrocytes was investigated in vitro using rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. The assessment of mitochondrial respiration or lactate dehydrogenase release has shown a dose-dependent decrease in the viability of astrocytes treated with 6-OHDA, which coincided with DNA fragmentation and the changes in cellular morphology. This was a consequence of the oxidative stress mediated by 6-OHDA autoxidation products hydrogen peroxide, superoxide anion, and hydroxyl radical. Both FeSO(4) and FeCl(3) markedly alleviated detrimental effects of 6-OHDA treatment, while MgSO(4) was without effect. The protective action of iron was neutralized by a membrane-permeable iron chelator o-phenanthroline, which also augmented astrocyte killing in the absence of exogenous iron. The mechanisms responsible for iron-mediated protection of astrocytes did not involve interference with either 6-OHDA autoxidation, hydrogen peroxide toxicity, or 6-OHDA-induced activation of extracellular signal-regulated kinase. Finally, the addition of iron potentiated and its chelation blocked 6-OHDA toxicity towards neuronal PC12 cells, suggesting the opposite roles for this transition metal in regulating the survival of astrocytes and dopaminergic neurons.
PB  - Elsevier Ltd.
T2  - Neuropharmacology
T1  - Iron protects astrocytes from 6-hydroxydopamine toxicity
IS  - 5
VL  - 48
DO  - 10.1016/j.neuropharm.2004.12.003
SP  - 720
EP  - 731
ER  - 

@article{
author = "Zogović, Nevena and Mladenović, Aleksandra and Perović, Milka and Harhaji-Trajković, Ljubica and Miljković, Đorđe and Trajković, Vladimir",
year = "2005",
abstract = "The role of iron in 6-hydroxydopamine (6-OHDA) toxicity towards astrocytes was investigated in vitro using rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. The assessment of mitochondrial respiration or lactate dehydrogenase release has shown a dose-dependent decrease in the viability of astrocytes treated with 6-OHDA, which coincided with DNA fragmentation and the changes in cellular morphology. This was a consequence of the oxidative stress mediated by 6-OHDA autoxidation products hydrogen peroxide, superoxide anion, and hydroxyl radical. Both FeSO(4) and FeCl(3) markedly alleviated detrimental effects of 6-OHDA treatment, while MgSO(4) was without effect. The protective action of iron was neutralized by a membrane-permeable iron chelator o-phenanthroline, which also augmented astrocyte killing in the absence of exogenous iron. The mechanisms responsible for iron-mediated protection of astrocytes did not involve interference with either 6-OHDA autoxidation, hydrogen peroxide toxicity, or 6-OHDA-induced activation of extracellular signal-regulated kinase. Finally, the addition of iron potentiated and its chelation blocked 6-OHDA toxicity towards neuronal PC12 cells, suggesting the opposite roles for this transition metal in regulating the survival of astrocytes and dopaminergic neurons.",
publisher = "Elsevier Ltd.",
journal = "Neuropharmacology",
title = "Iron protects astrocytes from 6-hydroxydopamine toxicity",
number = "5",
volume = "48",
doi = "10.1016/j.neuropharm.2004.12.003",
pages = "720-731"
}

Zogović, N., Mladenović, A., Perović, M., Harhaji-Trajković, L., Miljković, Đ.,& Trajković, V.. (2005). Iron protects astrocytes from 6-hydroxydopamine toxicity. in Neuropharmacology
Elsevier Ltd.., 48(5), 720-731.
https://doi.org/10.1016/j.neuropharm.2004.12.003

Zogović N, Mladenović A, Perović M, Harhaji-Trajković L, Miljković Đ, Trajković V. Iron protects astrocytes from 6-hydroxydopamine toxicity. in Neuropharmacology. 2005;48(5):720-731.
doi:10.1016/j.neuropharm.2004.12.003 .

Zogović, Nevena, Mladenović, Aleksandra, Perović, Milka, Harhaji-Trajković, Ljubica, Miljković, Đorđe, Trajković, Vladimir, "Iron protects astrocytes from 6-hydroxydopamine toxicity" in Neuropharmacology, 48, no. 5 (2005):720-731,
https://doi.org/10.1016/j.neuropharm.2004.12.003 . .

TY  - JOUR
AU  - Marković, Milos
AU  - Knežević, Nikola Z
AU  - Momčilović, Miljana
AU  - Grgurić-Sipka, Sanja R
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir S
AU  - Mostarica-Stojković, Marija B
AU  - Sabo, Tibor J
AU  - Miljković, Đorđe
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1696
AB  - There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties
IS  - 1-2
VL  - 517
EP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1696
ER  - 

@article{
author = "Marković, Milos and Knežević, Nikola Z and Momčilović, Miljana and Grgurić-Sipka, Sanja R and Harhaji-Trajković, Ljubica and Trajković, Vladimir S and Mostarica-Stojković, Marija B and Sabo, Tibor J and Miljković, Đorđe",
year = "2005",
abstract = "There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties",
number = "1-2",
volume = "517",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1696"
}

Marković, M., Knežević, N. Z., Momčilović, M., Grgurić-Sipka, S. R., Harhaji-Trajković, L., Trajković, V. S., Mostarica-Stojković, M. B., Sabo, T. J.,& Miljković, Đ.. (2005). [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties. in European Journal of Pharmacology, 517(1-2).
https://hdl.handle.net/21.15107/rcub_ibiss_1696

Marković M, Knežević NZ, Momčilović M, Grgurić-Sipka SR, Harhaji-Trajković L, Trajković VS, Mostarica-Stojković MB, Sabo TJ, Miljković Đ. [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties. in European Journal of Pharmacology. 2005;517(1-2):null-34.
https://hdl.handle.net/21.15107/rcub_ibiss_1696 .

Marković, Milos, Knežević, Nikola Z, Momčilović, Miljana, Grgurić-Sipka, Sanja R, Harhaji-Trajković, Ljubica, Trajković, Vladimir S, Mostarica-Stojković, Marija B, Sabo, Tibor J, Miljković, Đorđe, "[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties" in European Journal of Pharmacology, 517, no. 1-2 (2005),
https://hdl.handle.net/21.15107/rcub_ibiss_1696 .

TY  - CONF
AU  - Zogović, Nevena
AU  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Miljković, Đorđe
AU  - Trajković, Vladimir S
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1640
AB  - Treatment with 6-hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6-Hydroxydopamine-treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6-hydroxydopamine autooxidation products H2O2, O-2, and -OH, but not by cell-derived or chemically generated anti-apoptotic free radical nitric oxide. Finally, 6-hydroxydopamine activated extracellular signal-regulated kinase in astrocytes and selective inhibitor of extracellular signal-regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6-hydroxydopamine-triggered oxidative stress induces extracellular signal-regulated kinase-dependent apoptotic death of astrocytes.
C3  - Biophysics from Molecules to Brain: in Memory of Radoslav K. Andjus
T1  - The mechanisms of 6-hydroxydopamineInduced astrocyte death
IS  - null
VL  - 1048
EP  - 405
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1640
ER  - 

@conference{
author = "Zogović, Nevena and Mladenović, Aleksandra and Perović, Milka and Miljković, Đorđe and Trajković, Vladimir S",
year = "2005",
abstract = "Treatment with 6-hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6-Hydroxydopamine-treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6-hydroxydopamine autooxidation products H2O2, O-2, and -OH, but not by cell-derived or chemically generated anti-apoptotic free radical nitric oxide. Finally, 6-hydroxydopamine activated extracellular signal-regulated kinase in astrocytes and selective inhibitor of extracellular signal-regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6-hydroxydopamine-triggered oxidative stress induces extracellular signal-regulated kinase-dependent apoptotic death of astrocytes.",
journal = "Biophysics from Molecules to Brain: in Memory of Radoslav K. Andjus",
title = "The mechanisms of 6-hydroxydopamineInduced astrocyte death",
number = "null",
volume = "1048",
pages = "405",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1640"
}

Zogović, N., Mladenović, A., Perović, M., Miljković, Đ.,& Trajković, V. S.. (2005). The mechanisms of 6-hydroxydopamineInduced astrocyte death. in Biophysics from Molecules to Brain: in Memory of Radoslav K. Andjus, 1048(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1640

Zogović N, Mladenović A, Perović M, Miljković Đ, Trajković VS. The mechanisms of 6-hydroxydopamineInduced astrocyte death. in Biophysics from Molecules to Brain: in Memory of Radoslav K. Andjus. 2005;1048(null):null-405.
https://hdl.handle.net/21.15107/rcub_ibiss_1640 .

Zogović, Nevena, Mladenović, Aleksandra, Perović, Milka, Miljković, Đorđe, Trajković, Vladimir S, "The mechanisms of 6-hydroxydopamineInduced astrocyte death" in Biophysics from Molecules to Brain: in Memory of Radoslav K. Andjus, 1048, no. null (2005),
https://hdl.handle.net/21.15107/rcub_ibiss_1640 .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
AU  - Momčilović, Miljana
AU  - Maksimović-Ivanić, Danijela
AU  - Stošić-Grujičić, Stanislava
AU  - Trajković, Vladimir S
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1686
AB  - The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations of interferon-gamma, tumor necrosis factor-alpha, and IL-1 beta. The induction of iNOS by IL-17 was preceded by phosphorylation of p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release. IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease.
T2  - Cellular and Molecular Life Sciences
T1  - Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells
IS  - 22
VL  - 62
DO  - 10.1007/s00018-005-5259-0
SP  - 2668
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1686
ER  - 

@article{
author = "Miljković, Đorđe and Stojanović, Ivana D. and Momčilović, Miljana and Maksimović-Ivanić, Danijela and Stošić-Grujičić, Stanislava and Trajković, Vladimir S",
year = "2005",
abstract = "The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations of interferon-gamma, tumor necrosis factor-alpha, and IL-1 beta. The induction of iNOS by IL-17 was preceded by phosphorylation of p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release. IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease.",
journal = "Cellular and Molecular Life Sciences",
title = "Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells",
number = "22",
volume = "62",
doi = "10.1007/s00018-005-5259-0",
pages = "2668",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1686"
}

Miljković, Đ., Stojanović, I. D., Momčilović, M., Maksimović-Ivanić, D., Stošić-Grujičić, S.,& Trajković, V. S.. (2005). Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells. in Cellular and Molecular Life Sciences, 62(22), 2668.
https://doi.org/10.1007/s00018-005-5259-0
https://hdl.handle.net/21.15107/rcub_ibiss_1686

Miljković Đ, Stojanović ID, Momčilović M, Maksimović-Ivanić D, Stošić-Grujičić S, Trajković VS. Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells. in Cellular and Molecular Life Sciences. 2005;62(22):2668.
doi:10.1007/s00018-005-5259-0
https://hdl.handle.net/21.15107/rcub_ibiss_1686 .

Miljković, Đorđe, Stojanović, Ivana D., Momčilović, Miljana, Maksimović-Ivanić, Danijela, Stošić-Grujičić, Stanislava, Trajković, Vladimir S, "Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells" in Cellular and Molecular Life Sciences, 62, no. 22 (2005):2668,
https://doi.org/10.1007/s00018-005-5259-0 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1686 .

TY  - CONF
AU  - Marković, Milos
AU  - Miljković, Đorđe
AU  - Trajković, Vladimir S
AU  - Mostarica-Stojković, Marija B
AU  - Stošić-Grujičić, Stanislava
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1695
C3  - Inflammation Research
T1  - Prevention of experimental autoimmune diabetes with complete Freund's adjuvant in mice - role of nitric oxide
IS  - null
VL  - 54
EP  - S132
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1695
ER  - 

@conference{
author = "Marković, Milos and Miljković, Đorđe and Trajković, Vladimir S and Mostarica-Stojković, Marija B and Stošić-Grujičić, Stanislava",
year = "2005",
journal = "Inflammation Research",
title = "Prevention of experimental autoimmune diabetes with complete Freund's adjuvant in mice - role of nitric oxide",
number = "null",
volume = "54",
pages = "S132",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1695"
}

Marković, M., Miljković, Đ., Trajković, V. S., Mostarica-Stojković, M. B.,& Stošić-Grujičić, S.. (2005). Prevention of experimental autoimmune diabetes with complete Freund's adjuvant in mice - role of nitric oxide. in Inflammation Research, 54(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1695

Marković M, Miljković Đ, Trajković VS, Mostarica-Stojković MB, Stošić-Grujičić S. Prevention of experimental autoimmune diabetes with complete Freund's adjuvant in mice - role of nitric oxide. in Inflammation Research. 2005;54(null):null-S132.
https://hdl.handle.net/21.15107/rcub_ibiss_1695 .

Marković, Milos, Miljković, Đorđe, Trajković, Vladimir S, Mostarica-Stojković, Marija B, Stošić-Grujičić, Stanislava, "Prevention of experimental autoimmune diabetes with complete Freund's adjuvant in mice - role of nitric oxide" in Inflammation Research, 54, no. null (2005),
https://hdl.handle.net/21.15107/rcub_ibiss_1695 .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
AU  - Sajić, Marija
AU  - Vucković, Olivera
AU  - Harhaji-Trajković, Ljubica
AU  - Marković, Milos
AU  - Trajković, Vladimir S
PY  - 2004
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1741
AB  - Given the important role of gaseous free radical nitric oxide (NO) in tumor cell biology, we investigated the ability of the anti-cancer drugs 5-Aza-2'-deoxycytidine (ADC) and paclitaxel to modulate NO production in mouse L929 fibrosarcoma cells. Both drugs reduced IFN-gamma-stimulated NO release in cultures of L929 and primary fibroblasts, but not in mouse peritoneal macrophages. The inhibitory effect was due to the reduced expression of inducible NO synthase (iNOS), the enzyme responsible for cytokine-induced intracellular NO synthesis, as both agents markedly suppressed the interferon-ganuna (IFN-gamma)-triggered increase in iNOS concentration in L929 cells. In addition, ADC and paclitaxel prevented the FFN-gamma-triggered activation of p44/p42 mitogen-activated protein (MAP) kinase in L929 fibroblasts, suggesting a possible mechanism for the observed inhibition of iNOS expression. These results might have important implications for the therapeutic effect of ADC and paclitaxel, since their inhibitory action on NO release partly neutralized the NO-dependent toxicity of IFN-gamma on L929 fibrosarcoma cells. (C) 2003 Elsevier B.V All rights reserved.
T2  - European Journal of Pharmacology
T1  - 5-Aza-2 '-deoxycytidine and paclitaxel inhibit inducible nitric oxide synthase activation in fibrosarcoma cells
IS  - 1-3
VL  - 485
DO  - 10.1016/j.ejphar.2003.11.057
SP  - 81
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1741
ER  - 

@article{
author = "Miljković, Đorđe and Stojanović, Ivana D. and Sajić, Marija and Vucković, Olivera and Harhaji-Trajković, Ljubica and Marković, Milos and Trajković, Vladimir S",
year = "2004",
abstract = "Given the important role of gaseous free radical nitric oxide (NO) in tumor cell biology, we investigated the ability of the anti-cancer drugs 5-Aza-2'-deoxycytidine (ADC) and paclitaxel to modulate NO production in mouse L929 fibrosarcoma cells. Both drugs reduced IFN-gamma-stimulated NO release in cultures of L929 and primary fibroblasts, but not in mouse peritoneal macrophages. The inhibitory effect was due to the reduced expression of inducible NO synthase (iNOS), the enzyme responsible for cytokine-induced intracellular NO synthesis, as both agents markedly suppressed the interferon-ganuna (IFN-gamma)-triggered increase in iNOS concentration in L929 cells. In addition, ADC and paclitaxel prevented the FFN-gamma-triggered activation of p44/p42 mitogen-activated protein (MAP) kinase in L929 fibroblasts, suggesting a possible mechanism for the observed inhibition of iNOS expression. These results might have important implications for the therapeutic effect of ADC and paclitaxel, since their inhibitory action on NO release partly neutralized the NO-dependent toxicity of IFN-gamma on L929 fibrosarcoma cells. (C) 2003 Elsevier B.V All rights reserved.",
journal = "European Journal of Pharmacology",
title = "5-Aza-2 '-deoxycytidine and paclitaxel inhibit inducible nitric oxide synthase activation in fibrosarcoma cells",
number = "1-3",
volume = "485",
doi = "10.1016/j.ejphar.2003.11.057",
pages = "81-88",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1741"
}

Miljković, Đ., Stojanović, I. D., Sajić, M., Vucković, O., Harhaji-Trajković, L., Marković, M.,& Trajković, V. S.. (2004). 5-Aza-2 '-deoxycytidine and paclitaxel inhibit inducible nitric oxide synthase activation in fibrosarcoma cells. in European Journal of Pharmacology, 485(1-3), 81-88.
https://doi.org/10.1016/j.ejphar.2003.11.057
https://hdl.handle.net/21.15107/rcub_ibiss_1741

Miljković Đ, Stojanović ID, Sajić M, Vucković O, Harhaji-Trajković L, Marković M, Trajković VS. 5-Aza-2 '-deoxycytidine and paclitaxel inhibit inducible nitric oxide synthase activation in fibrosarcoma cells. in European Journal of Pharmacology. 2004;485(1-3):81-88.
doi:10.1016/j.ejphar.2003.11.057
https://hdl.handle.net/21.15107/rcub_ibiss_1741 .

Miljković, Đorđe, Stojanović, Ivana D., Sajić, Marija, Vucković, Olivera, Harhaji-Trajković, Ljubica, Marković, Milos, Trajković, Vladimir S, "5-Aza-2 '-deoxycytidine and paclitaxel inhibit inducible nitric oxide synthase activation in fibrosarcoma cells" in European Journal of Pharmacology, 485, no. 1-3 (2004):81-88,
https://doi.org/10.1016/j.ejphar.2003.11.057 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1741 .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Vucković, Olivera
AU  - Harhaji-Trajković, Ljubica
AU  - Nikolić, Zoran M
AU  - Trajković, Vladimir S
AU  - Mostarica-Stojković, Marija B
PY  - 2004
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1735
AB  - Taxol is a microtubule-stabilizing agent that has recently been shown effective in the treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. As astrocytes could modulate central nervous system (CNS) autoimmunity through inducible nitric oxide synthase (iNOS)-mediated production of immunoregulatory free radical nitric oxide (NO), we investigated the effect of taxol on NO synthesis in rat astrocytes. Taxol, either alone or in combination with interferon-gamma, induced NO generation in primary astrocytes and astrocytoma C6 cells in a dose- and time-dependent manner. Accordingly, the drug markedly up-regulated the expression of both iNOS mRNA and protein in astrocytes. The observed effect of taxol was mediated through induction of iNOS transcription factors NF-kappaB and IRF-1, and required the activation of p38 MAP kinase and JNK. Finally, NO release by taxol-stimulated astrocytes was blocked with the microtubule-depolymerizing agent colchicine, suggesting the involvement of a microtubule-stabilizing activity of taxol in the observed effect.
T2  - Cellular and Molecular Life Sciences
T1  - Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of MAP kinases and NF-kappa B
IS  - 10
VL  - 61
EP  - 1175
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1735
ER  - 

@article{
author = "Stojanović, Ivana D. and Miljković, Đorđe and Vucković, Olivera and Harhaji-Trajković, Ljubica and Nikolić, Zoran M and Trajković, Vladimir S and Mostarica-Stojković, Marija B",
year = "2004",
abstract = "Taxol is a microtubule-stabilizing agent that has recently been shown effective in the treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. As astrocytes could modulate central nervous system (CNS) autoimmunity through inducible nitric oxide synthase (iNOS)-mediated production of immunoregulatory free radical nitric oxide (NO), we investigated the effect of taxol on NO synthesis in rat astrocytes. Taxol, either alone or in combination with interferon-gamma, induced NO generation in primary astrocytes and astrocytoma C6 cells in a dose- and time-dependent manner. Accordingly, the drug markedly up-regulated the expression of both iNOS mRNA and protein in astrocytes. The observed effect of taxol was mediated through induction of iNOS transcription factors NF-kappaB and IRF-1, and required the activation of p38 MAP kinase and JNK. Finally, NO release by taxol-stimulated astrocytes was blocked with the microtubule-depolymerizing agent colchicine, suggesting the involvement of a microtubule-stabilizing activity of taxol in the observed effect.",
journal = "Cellular and Molecular Life Sciences",
title = "Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of MAP kinases and NF-kappa B",
number = "10",
volume = "61",
pages = "1175",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1735"
}

Stojanović, I. D., Miljković, Đ., Vucković, O., Harhaji-Trajković, L., Nikolić, Z. M., Trajković, V. S.,& Mostarica-Stojković, M. B.. (2004). Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of MAP kinases and NF-kappa B. in Cellular and Molecular Life Sciences, 61(10).
https://hdl.handle.net/21.15107/rcub_ibiss_1735

Stojanović ID, Miljković Đ, Vucković O, Harhaji-Trajković L, Nikolić ZM, Trajković VS, Mostarica-Stojković MB. Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of MAP kinases and NF-kappa B. in Cellular and Molecular Life Sciences. 2004;61(10):null-1175.
https://hdl.handle.net/21.15107/rcub_ibiss_1735 .

Stojanović, Ivana D., Miljković, Đorđe, Vucković, Olivera, Harhaji-Trajković, Ljubica, Nikolić, Zoran M, Trajković, Vladimir S, Mostarica-Stojković, Marija B, "Taxol activates inducible nitric oxide synthase in rat astrocytes: the role of MAP kinases and NF-kappa B" in Cellular and Molecular Life Sciences, 61, no. 10 (2004),
https://hdl.handle.net/21.15107/rcub_ibiss_1735 .

TY  - JOUR
AU  - Trajković, Vladimir S
AU  - Vucković, Olivera
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Đorđe
AU  - Popadić, Dušan M.
AU  - Marković, Miloš
AU  - Bumbaširević, Vesna D
AU  - Backović, Aleksandar
AU  - Stojanović, Ivana D.
AU  - Harhaji-Trajković, Ljubica
AU  - Ramić, Zorica D.
AU  - Mostarica-Stojković, Marija
PY  - 2004
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1682
AB  - Although astrocytes presumably participate in maintaining the immune privilege of the central nervous system (CNS), the mechanisms behind their immunoregulatory properties are still largely undefined. In this study, we describe the development of regulatory T cells upon contact with astrocytes. Rat T cells pre-incubated with astrocytes completely lost the ability to proliferate in response to mitogenic stimuli. The cells were blocked in G0/G1 phase of the cell cycle, expressed less IL-2R, and produced significantly lower amounts of interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2), IL-10, or tumor necrosis factor (TNF). These anergic cells completely prevented mitogen-induced growth of normal T lymphocytes, as well as CNS antigen-driven proliferation of autoreactive T cells. The suppressive activity resided in both CD4(+) and CD8(+) T-cell compartments. Heat-sensitive soluble T-cell factors, not including transforming growth factor-beta (TGF-beta) or IL-10, were solely responsible for the observed suppression, as well as for the transfer of suppressive activity to normal T cells. The administration of astrocyte-induced regulatory T cells markedly alleviated CNS inflammation and clinical symptoms of CNS autoimmunity in rats with experimental allergic encephalomyelitis. Finally, the cells with suppressive properties were readily generated from human lymphocytes after contact with astrocytes. Taken together, these data indicate that astrocyte-induced regulatory T cells might represent an important mechanism for self-limitation of excessive inflammation in the brain. (C) 2004 Wiley-Liss, Inc.
T2  - Glia
T1  - Astrocyte-induced regulatory T cells mitigate CNS autoimmunity
IS  - 2
VL  - 47
DO  - 10.1002/glia.20046
SP  - 168
EP  - 179
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1682
ER  - 

@article{
author = "Trajković, Vladimir S and Vucković, Olivera and Stošić-Grujičić, Stanislava and Miljković, Đorđe and Popadić, Dušan M. and Marković, Miloš and Bumbaširević, Vesna D and Backović, Aleksandar and Stojanović, Ivana D. and Harhaji-Trajković, Ljubica and Ramić, Zorica D. and Mostarica-Stojković, Marija",
year = "2004",
abstract = "Although astrocytes presumably participate in maintaining the immune privilege of the central nervous system (CNS), the mechanisms behind their immunoregulatory properties are still largely undefined. In this study, we describe the development of regulatory T cells upon contact with astrocytes. Rat T cells pre-incubated with astrocytes completely lost the ability to proliferate in response to mitogenic stimuli. The cells were blocked in G0/G1 phase of the cell cycle, expressed less IL-2R, and produced significantly lower amounts of interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2), IL-10, or tumor necrosis factor (TNF). These anergic cells completely prevented mitogen-induced growth of normal T lymphocytes, as well as CNS antigen-driven proliferation of autoreactive T cells. The suppressive activity resided in both CD4(+) and CD8(+) T-cell compartments. Heat-sensitive soluble T-cell factors, not including transforming growth factor-beta (TGF-beta) or IL-10, were solely responsible for the observed suppression, as well as for the transfer of suppressive activity to normal T cells. The administration of astrocyte-induced regulatory T cells markedly alleviated CNS inflammation and clinical symptoms of CNS autoimmunity in rats with experimental allergic encephalomyelitis. Finally, the cells with suppressive properties were readily generated from human lymphocytes after contact with astrocytes. Taken together, these data indicate that astrocyte-induced regulatory T cells might represent an important mechanism for self-limitation of excessive inflammation in the brain. (C) 2004 Wiley-Liss, Inc.",
journal = "Glia",
title = "Astrocyte-induced regulatory T cells mitigate CNS autoimmunity",
number = "2",
volume = "47",
doi = "10.1002/glia.20046",
pages = "168-179",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1682"
}

Trajković, V. S., Vucković, O., Stošić-Grujičić, S., Miljković, Đ., Popadić, D. M., Marković, M., Bumbaširević, V. D., Backović, A., Stojanović, I. D., Harhaji-Trajković, L., Ramić, Z. D.,& Mostarica-Stojković, M.. (2004). Astrocyte-induced regulatory T cells mitigate CNS autoimmunity. in Glia, 47(2), 168-179.
https://doi.org/10.1002/glia.20046
https://hdl.handle.net/21.15107/rcub_ibiss_1682

Trajković VS, Vucković O, Stošić-Grujičić S, Miljković Đ, Popadić DM, Marković M, Bumbaširević VD, Backović A, Stojanović ID, Harhaji-Trajković L, Ramić ZD, Mostarica-Stojković M. Astrocyte-induced regulatory T cells mitigate CNS autoimmunity. in Glia. 2004;47(2):168-179.
doi:10.1002/glia.20046
https://hdl.handle.net/21.15107/rcub_ibiss_1682 .

Trajković, Vladimir S, Vucković, Olivera, Stošić-Grujičić, Stanislava, Miljković, Đorđe, Popadić, Dušan M., Marković, Miloš, Bumbaširević, Vesna D, Backović, Aleksandar, Stojanović, Ivana D., Harhaji-Trajković, Ljubica, Ramić, Zorica D., Mostarica-Stojković, Marija, "Astrocyte-induced regulatory T cells mitigate CNS autoimmunity" in Glia, 47, no. 2 (2004):168-179,
https://doi.org/10.1002/glia.20046 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1682 .

TY  - JOUR
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
AU  - Maksimović-Ivanić, Danijela
AU  - Trajković, Vladimir S
PY  - 2004
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1732
AB  - Oxidative stress makes an important contribution to the development of autoimmune diabetes. We therefore tested the possible therapeutic value of two anti-oxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbarnate (PDTC), in the animal model of diabetes induced in susceptible DA rats by multiple low doses of streptozotocin (MLD-SZ, 20 mg/kg/day for 5 days). Administration of either BHA, or PDTC (50 mg/kg/day for 7 days), after finishing MLD-SZ injections, attenuated both the development of hyperglycemia and insulitis. Ex vivo analysis revealed that BHA treatment reduced the proliferation of autoreactive lymphocytes and down-regulated their adhesion to endothelium. In addition, BHA markedly attenuated the production of proinflammatory cytokines 1L-1beta and TNF-alpha by both islets of pancreas and peritoneal macrophages. In parallel, macrophage release of cytotoxic oxygen and nitrogen intermediates superoxide anion (O-2.(-)) and nitric oxide (NO.), respectively, was significantly inhibited. Finally, BHA treatment reduced intrapancreatic expression of inducible NO synthase (iNOS) and consequent production of NO. by pancreatic islets. Together, these data indicate that antioxidant agents might be a feasible therapeutic tools to interfere with development of autoimmune diabetes at multiple levels, including lymphocyte proliferation and adhesion, as well as the production of proinflammatory and cytotoxic mediators. (C) 2004 Elsevier Ltd. All rights reserved.
T2  - Journal of Autoimmunity
T1  - Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes
IS  - 4
VL  - 22
DO  - 10.1016/j.jaut.2004.01.005
SP  - 267
EP  - 276
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1732
ER  - 

@article{
author = "Stošić-Grujičić, Stanislava and Miljković, Đorđe and Stojanović, Ivana D. and Maksimović-Ivanić, Danijela and Trajković, Vladimir S",
year = "2004",
abstract = "Oxidative stress makes an important contribution to the development of autoimmune diabetes. We therefore tested the possible therapeutic value of two anti-oxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbarnate (PDTC), in the animal model of diabetes induced in susceptible DA rats by multiple low doses of streptozotocin (MLD-SZ, 20 mg/kg/day for 5 days). Administration of either BHA, or PDTC (50 mg/kg/day for 7 days), after finishing MLD-SZ injections, attenuated both the development of hyperglycemia and insulitis. Ex vivo analysis revealed that BHA treatment reduced the proliferation of autoreactive lymphocytes and down-regulated their adhesion to endothelium. In addition, BHA markedly attenuated the production of proinflammatory cytokines 1L-1beta and TNF-alpha by both islets of pancreas and peritoneal macrophages. In parallel, macrophage release of cytotoxic oxygen and nitrogen intermediates superoxide anion (O-2.(-)) and nitric oxide (NO.), respectively, was significantly inhibited. Finally, BHA treatment reduced intrapancreatic expression of inducible NO synthase (iNOS) and consequent production of NO. by pancreatic islets. Together, these data indicate that antioxidant agents might be a feasible therapeutic tools to interfere with development of autoimmune diabetes at multiple levels, including lymphocyte proliferation and adhesion, as well as the production of proinflammatory and cytotoxic mediators. (C) 2004 Elsevier Ltd. All rights reserved.",
journal = "Journal of Autoimmunity",
title = "Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes",
number = "4",
volume = "22",
doi = "10.1016/j.jaut.2004.01.005",
pages = "267-276",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1732"
}

Stošić-Grujičić, S., Miljković, Đ., Stojanović, I. D., Maksimović-Ivanić, D.,& Trajković, V. S.. (2004). Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes. in Journal of Autoimmunity, 22(4), 267-276.
https://doi.org/10.1016/j.jaut.2004.01.005
https://hdl.handle.net/21.15107/rcub_ibiss_1732

Stošić-Grujičić S, Miljković Đ, Stojanović ID, Maksimović-Ivanić D, Trajković VS. Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes. in Journal of Autoimmunity. 2004;22(4):267-276.
doi:10.1016/j.jaut.2004.01.005
https://hdl.handle.net/21.15107/rcub_ibiss_1732 .

Stošić-Grujičić, Stanislava, Miljković, Đorđe, Stojanović, Ivana D., Maksimović-Ivanić, Danijela, Trajković, Vladimir S, "Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes" in Journal of Autoimmunity, 22, no. 4 (2004):267-276,
https://doi.org/10.1016/j.jaut.2004.01.005 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1732 .

TY  - JOUR
AU  - Đinović, Vesna M
AU  - Momčilović, Miljana
AU  - Grgurić-Sipka, Sanja R
AU  - Trajković, Vladimir S
AU  - Mostarica-Stojković, Marija B
AU  - Miljković, Đorđe
AU  - Sabo, Tibor J
PY  - 2004
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1723
AB  - A novel class of ruthenium (111) complexes of formulas K[Ru(sar)(2)Cl-2] - 1/2HO and K-2[Ru(dmgly)Cl-4] . 1/2H(2)O, containing biden2 tate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dnigly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmglY)(2)Cl-2], [Pt(sar)(2)Br-2] and [Pt(dmgly)(2)Br-2] on rat astrocytoma C6 cells in vitro. Among these complexes only K-2[Ru(dmglY)Cl-4].2H(2)O and [Pt(dMgIY)(2)Br-2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K-2[Ru(dmgly)Cl4] .2H20 was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K,[Ru(dmglY)Cl-4] - 2H(2)O could be a promising agent for developing therapeutics against astrocytomas. (C) 2004 Elsevier Inc. All rights reserved.
T2  - Journal of Inorganic Biochemistry
T1  - Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes
IS  - 12
VL  - 98
EP  - 2173
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1723
ER  - 

@article{
author = "Đinović, Vesna M and Momčilović, Miljana and Grgurić-Sipka, Sanja R and Trajković, Vladimir S and Mostarica-Stojković, Marija B and Miljković, Đorđe and Sabo, Tibor J",
year = "2004",
abstract = "A novel class of ruthenium (111) complexes of formulas K[Ru(sar)(2)Cl-2] - 1/2HO and K-2[Ru(dmgly)Cl-4] . 1/2H(2)O, containing biden2 tate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dnigly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmglY)(2)Cl-2], [Pt(sar)(2)Br-2] and [Pt(dmgly)(2)Br-2] on rat astrocytoma C6 cells in vitro. Among these complexes only K-2[Ru(dmglY)Cl-4].2H(2)O and [Pt(dMgIY)(2)Br-2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K-2[Ru(dmgly)Cl4] .2H20 was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K,[Ru(dmglY)Cl-4] - 2H(2)O could be a promising agent for developing therapeutics against astrocytomas. (C) 2004 Elsevier Inc. All rights reserved.",
journal = "Journal of Inorganic Biochemistry",
title = "Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes",
number = "12",
volume = "98",
pages = "2173",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1723"
}

Đinović, V. M., Momčilović, M., Grgurić-Sipka, S. R., Trajković, V. S., Mostarica-Stojković, M. B., Miljković, Đ.,& Sabo, T. J.. (2004). Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes. in Journal of Inorganic Biochemistry, 98(12).
https://hdl.handle.net/21.15107/rcub_ibiss_1723

Đinović VM, Momčilović M, Grgurić-Sipka SR, Trajković VS, Mostarica-Stojković MB, Miljković Đ, Sabo TJ. Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes. in Journal of Inorganic Biochemistry. 2004;98(12):null-2173.
https://hdl.handle.net/21.15107/rcub_ibiss_1723 .

Đinović, Vesna M, Momčilović, Miljana, Grgurić-Sipka, Sanja R, Trajković, Vladimir S, Mostarica-Stojković, Marija B, Miljković, Đorđe, Sabo, Tibor J, "Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes" in Journal of Inorganic Biochemistry, 98, no. 12 (2004),
https://hdl.handle.net/21.15107/rcub_ibiss_1723 .