TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović-Matić, Svetlana
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović-Stojanov, Sofija
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5660
AB  - Oxidative stress. cell damage and cell death underlies the etiology of liver damage/dysfunction  in  diabetes.  Bigh  Mobility  Group  Box 1 (HMGB1) is a nuclear protein that is  released  from damaged/stressed  liver cells during, diabetes and  contributes to oxidative  stresse-mediated autophagy  an cell death/survival. Since ethyl pyruvate (EP) an HMGB1 relase/expession and autophagy in the liver of diabetic rats. Diabetes was indused by streptozotocin(65mg/kg). Pretreated group of diabetes rats- (EP+D) startedl treatment  with EP (80mg/kg/daily) three·days before
diabetes induction,  while  in  the  second  group  (D+EP}  treatment  start   ten  days after diabetes induuction. In compcarison with D+EP group, EP+D group had better glycemic  status  and  higher  activity  of  antioxidative enzyme  SOD  and CAT in diabetic  liver.  According  to  western  immunoblot   analyses,  EP+D  group   sliowed higher     expression     of     extracellular    HMGB l     in    comparison      with D+EP. Consequently  detected increase in HMGB1/RAGE interactions in EP+D group were followed  by higher expression of LC3-II, HMGB1/Beclin 1 interaction and activation  of  autophagy.  Expression  of  LC3-II  and   HMGB1/Beclin 1 interaction were  at  the  control  level  in  D+EP.  Preserved  liver   morphology  in  both  EP   treated groups, observed  by  electron  microscopy,   implicated  existence   of   adaptive mechanisms  in EP+D  group.  Further  analyses  showed that  protective autophagy (mitophagy) was enhanced in EP+D group compared with diabetic and D+EP groups. Thus treatment of  diabetic  patients  with  EP  may  constitute  a  new strategy for the treatment  of  diabetes related  tissue  injury.
PB  - Belgrade: Serbian Physiological Society
C3  - Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
T1  - Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver
SP  - 108
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5660
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović-Matić, Svetlana and Martinović, Vesna and Korać, Aleksandra and Jovanović-Stojanov, Sofija and Grigorov, Ilijana",
year = "2018",
abstract = "Oxidative stress. cell damage and cell death underlies the etiology of liver damage/dysfunction  in  diabetes.  Bigh  Mobility  Group  Box 1 (HMGB1) is a nuclear protein that is  released  from damaged/stressed  liver cells during, diabetes and  contributes to oxidative  stresse-mediated autophagy  an cell death/survival. Since ethyl pyruvate (EP) an HMGB1 relase/expession and autophagy in the liver of diabetic rats. Diabetes was indused by streptozotocin(65mg/kg). Pretreated group of diabetes rats- (EP+D) startedl treatment  with EP (80mg/kg/daily) three·days before
diabetes induction,  while  in  the  second  group  (D+EP}  treatment  start   ten  days after diabetes induuction. In compcarison with D+EP group, EP+D group had better glycemic  status  and  higher  activity  of  antioxidative enzyme  SOD  and CAT in diabetic  liver.  According  to  western  immunoblot   analyses,  EP+D  group   sliowed higher     expression     of     extracellular    HMGB l     in    comparison      with D+EP. Consequently  detected increase in HMGB1/RAGE interactions in EP+D group were followed  by higher expression of LC3-II, HMGB1/Beclin 1 interaction and activation  of  autophagy.  Expression  of  LC3-II  and   HMGB1/Beclin 1 interaction were  at  the  control  level  in  D+EP.  Preserved  liver   morphology  in  both  EP   treated groups, observed  by  electron  microscopy,   implicated  existence   of   adaptive mechanisms  in EP+D  group.  Further  analyses  showed that  protective autophagy (mitophagy) was enhanced in EP+D group compared with diabetic and D+EP groups. Thus treatment of  diabetic  patients  with  EP  may  constitute  a  new strategy for the treatment  of  diabetes related  tissue  injury.",
publisher = "Belgrade: Serbian Physiological Society",
journal = "Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia",
title = "Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver",
pages = "108",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5660"
}

Petrović, A., Bogojević, D., Ivanović-Matić, S., Martinović, V., Korać, A., Jovanović-Stojanov, S.,& Grigorov, I.. (2018). Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
Belgrade: Serbian Physiological Society., 108.
https://hdl.handle.net/21.15107/rcub_ibiss_5660

Petrović A, Bogojević D, Ivanović-Matić S, Martinović V, Korać A, Jovanović-Stojanov S, Grigorov I. Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia. 2018;:108.
https://hdl.handle.net/21.15107/rcub_ibiss_5660 .

Petrović, Anja, Bogojević, Desanka, Ivanović-Matić, Svetlana, Martinović, Vesna, Korać, Aleksandra, Jovanović-Stojanov, Sofija, Grigorov, Ilijana, "Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver" in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia (2018):108,
https://hdl.handle.net/21.15107/rcub_ibiss_5660 .

TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović Stojanov, Sofija
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5237
AB  - Oxidative stress through changes in antioxidative enzyme activities, glutathione metabolism and lipid peroxidation, leads to cell damage and even cell death. These changes are integrated in the pathogenetic mechanisms of the long-term, specific complications of diabetes, such as neuropathy, retinopathy, cardiomyopathy, nephropathy and hepatopathy. Recent studies have shed light on new redox sensitive endogenous targets which are important regulators of oxidative stress-induced damage. HMGB1 is a nuclear chaperone with an inflammatory function when released in the extracellular space. Extracellular HMGB1, through interaction with TLR4 receptors in its oxidized state, and with RAGE in its reduced state, controls the equilibrium between apoptosis and autophagy. HMGB1 is  a redox sensitive protein with a potentially harmful role. We therefore analyzed the changes in HMGB1 regulated signaling pathways by immunoprecipitation and Western blot that can lead to cell death or cell survival in the liver of streptozotocin (STZ)-induced diabetic rats during decreased oxidative stress after melatonin administration, and when HMGB1 release was inhibited by ethyl pyruvate. Inhibition of HMGB1 release decreased both apoptosis and autophagy, and supported the unchanged state in liver cells in STZ-treated rats as compared to the control animals. The decrease in oxidative stress achieved with melatonin decreased HMGB1 driven apoptosis but upregulated HMGB1 regulated protective autophagy, mitophagy in particular as the second level of antioxidative defense which was detected by electron microscopy. It provided a selective advantage, minimizing oxidant insults when primary antioxidant activities are compromised during oxidative stress. This adaptation led to improved cell survival in the liver of STZ-treated rats. These results showed that modulation of the role of HMGB1 in the extracellular space that was achieved by a decrease in oxidative stress is more desirable than complete inhibition of its release because HMGB1 has a protective role against oxidative injuries in diabetic liver.
PB  - Belgrade: Serbian Society for Mitochondrial and Free Radical Physiology
C3  - Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia
T1  - The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver
SP  - 43
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5237
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović Matić, Svetlana and Martinović, Vesna and Korać, Aleksandra and Jovanović Stojanov, Sofija and Poznanović, Goran and Grigorov, Ilijana",
year = "2018",
abstract = "Oxidative stress through changes in antioxidative enzyme activities, glutathione metabolism and lipid peroxidation, leads to cell damage and even cell death. These changes are integrated in the pathogenetic mechanisms of the long-term, specific complications of diabetes, such as neuropathy, retinopathy, cardiomyopathy, nephropathy and hepatopathy. Recent studies have shed light on new redox sensitive endogenous targets which are important regulators of oxidative stress-induced damage. HMGB1 is a nuclear chaperone with an inflammatory function when released in the extracellular space. Extracellular HMGB1, through interaction with TLR4 receptors in its oxidized state, and with RAGE in its reduced state, controls the equilibrium between apoptosis and autophagy. HMGB1 is  a redox sensitive protein with a potentially harmful role. We therefore analyzed the changes in HMGB1 regulated signaling pathways by immunoprecipitation and Western blot that can lead to cell death or cell survival in the liver of streptozotocin (STZ)-induced diabetic rats during decreased oxidative stress after melatonin administration, and when HMGB1 release was inhibited by ethyl pyruvate. Inhibition of HMGB1 release decreased both apoptosis and autophagy, and supported the unchanged state in liver cells in STZ-treated rats as compared to the control animals. The decrease in oxidative stress achieved with melatonin decreased HMGB1 driven apoptosis but upregulated HMGB1 regulated protective autophagy, mitophagy in particular as the second level of antioxidative defense which was detected by electron microscopy. It provided a selective advantage, minimizing oxidant insults when primary antioxidant activities are compromised during oxidative stress. This adaptation led to improved cell survival in the liver of STZ-treated rats. These results showed that modulation of the role of HMGB1 in the extracellular space that was achieved by a decrease in oxidative stress is more desirable than complete inhibition of its release because HMGB1 has a protective role against oxidative injuries in diabetic liver.",
publisher = "Belgrade: Serbian Society for Mitochondrial and Free Radical Physiology",
journal = "Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia",
title = "The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver",
pages = "43",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5237"
}

Petrović, A., Bogojević, D., Ivanović Matić, S., Martinović, V., Korać, A., Jovanović Stojanov, S., Poznanović, G.,& Grigorov, I.. (2018). The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver. in Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia
Belgrade: Serbian Society for Mitochondrial and Free Radical Physiology., 43.
https://hdl.handle.net/21.15107/rcub_ibiss_5237

Petrović A, Bogojević D, Ivanović Matić S, Martinović V, Korać A, Jovanović Stojanov S, Poznanović G, Grigorov I. The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver. in Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia. 2018;:43.
https://hdl.handle.net/21.15107/rcub_ibiss_5237 .

Petrović, Anja, Bogojević, Desanka, Ivanović Matić, Svetlana, Martinović, Vesna, Korać, Aleksandra, Jovanović Stojanov, Sofija, Poznanović, Goran, Grigorov, Ilijana, "The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver" in Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia (2018):43,
https://hdl.handle.net/21.15107/rcub_ibiss_5237 .

TY  - JOUR
AU  - Jovanović Stojanov, Sofija
AU  - Martinović, Vesna
AU  - Bogojević, Desanka
AU  - Poznanović, Goran
AU  - Petrović, Anja
AU  - Ivanović Matić, Svetlana
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://link.springer.com/10.1007/s13105-018-0626-0
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29611132
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3068
AB  - Chronic inflammation plays an essential role in the development of diabetic complications. Understanding the molecular mechanisms that support inflammation is a prerequisite for the design of novel anti-inflammatory therapies. These would take into consideration circulating levels of cytokines and damage-associated molecular patterns (DAMPs) that include the high mobility group box 1 (HMGB1) protein which, in part, promotes the inflammatory response through TLR4 signaling. The liver, as the source of circulating cytokines and acute-phase proteins, contributes to the control of systemic inflammation. We previously found that liver injury in streptozotocin-induced diabetic rats correlated with the level of oxidative stress, increased expression of HMGB1, and with the activation of TLR4-mediated cell death pathways. In the present work, we examined the effects of ethyl pyruvate (EP), an inhibitor of HMGB1 release/expression, on the modulation of activation of the HMGB1/TLR4 inflammatory cascade in diabetic liver. We observed that increased expression of inflammatory markers, TNF-α, IL-6, and haptoglobin in diabetic liver was associated with increased HMGB1/TLR4 interaction, activation of MAPK (p38, ERK, JNK)/NF-κB p65 and JAK1/STAT3 signaling pathways, and with decreased expression of Nrf2-regulated antioxidative enzymes. The reduction in HMGB1 expression as the result of EP administration reduced the pro-inflammatory activity of HMGB1 and exerted a protective effect on diabetic liver, which was observed as improved liver histology and antioxidant and inflammatory statuses. Our results suggest that prevention of HMGB1 release and blockage of the HMGB/TLR4 axis represents a potentially effective therapeutic strategy aimed at ameliorating diabetes-induced inflammation and ensuing liver injury.
T2  - Journal of Physiology and Biochemistry
T1  - Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.
IS  - 2
VL  - 74
DO  - 10.1007/s13105-018-0626-0
SP  - 345
EP  - 358
ER  - 

@article{
author = "Jovanović Stojanov, Sofija and Martinović, Vesna and Bogojević, Desanka and Poznanović, Goran and Petrović, Anja and Ivanović Matić, Svetlana and Grigorov, Ilijana",
year = "2018",
abstract = "Chronic inflammation plays an essential role in the development of diabetic complications. Understanding the molecular mechanisms that support inflammation is a prerequisite for the design of novel anti-inflammatory therapies. These would take into consideration circulating levels of cytokines and damage-associated molecular patterns (DAMPs) that include the high mobility group box 1 (HMGB1) protein which, in part, promotes the inflammatory response through TLR4 signaling. The liver, as the source of circulating cytokines and acute-phase proteins, contributes to the control of systemic inflammation. We previously found that liver injury in streptozotocin-induced diabetic rats correlated with the level of oxidative stress, increased expression of HMGB1, and with the activation of TLR4-mediated cell death pathways. In the present work, we examined the effects of ethyl pyruvate (EP), an inhibitor of HMGB1 release/expression, on the modulation of activation of the HMGB1/TLR4 inflammatory cascade in diabetic liver. We observed that increased expression of inflammatory markers, TNF-α, IL-6, and haptoglobin in diabetic liver was associated with increased HMGB1/TLR4 interaction, activation of MAPK (p38, ERK, JNK)/NF-κB p65 and JAK1/STAT3 signaling pathways, and with decreased expression of Nrf2-regulated antioxidative enzymes. The reduction in HMGB1 expression as the result of EP administration reduced the pro-inflammatory activity of HMGB1 and exerted a protective effect on diabetic liver, which was observed as improved liver histology and antioxidant and inflammatory statuses. Our results suggest that prevention of HMGB1 release and blockage of the HMGB/TLR4 axis represents a potentially effective therapeutic strategy aimed at ameliorating diabetes-induced inflammation and ensuing liver injury.",
journal = "Journal of Physiology and Biochemistry",
title = "Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.",
number = "2",
volume = "74",
doi = "10.1007/s13105-018-0626-0",
pages = "345-358"
}

Jovanović Stojanov, S., Martinović, V., Bogojević, D., Poznanović, G., Petrović, A., Ivanović Matić, S.,& Grigorov, I.. (2018). Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.. in Journal of Physiology and Biochemistry, 74(2), 345-358.
https://doi.org/10.1007/s13105-018-0626-0

Jovanović Stojanov S, Martinović V, Bogojević D, Poznanović G, Petrović A, Ivanović Matić S, Grigorov I. Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.. in Journal of Physiology and Biochemistry. 2018;74(2):345-358.
doi:10.1007/s13105-018-0626-0 .

Jovanović Stojanov, Sofija, Martinović, Vesna, Bogojević, Desanka, Poznanović, Goran, Petrović, Anja, Ivanović Matić, Svetlana, Grigorov, Ilijana, "Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway." in Journal of Physiology and Biochemistry, 74, no. 2 (2018):345-358,
https://doi.org/10.1007/s13105-018-0626-0 . .

TY  - CONF
AU  - Jovanović Stojanov, Sofija
AU  - Grigorov, Ilijana
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Martinović, Vesna
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5246
AB  - Introduction: Oxidative stress and chronic low-grade inflammation in diabetes leads to liver injury. During diabetes, extracellular level of high-mobility group box-1 (HMGB1) protein increases. Considering that extracellular HMGB1 (eHMGB1) protein functions as an pro-inflammatory mediator, triggering inflammatory responses by promoting the expression of inflammatory cytokines, the aim of this study was to investigate its contribution to the maintenance of inflammatory condition in the liver of diabetic rats. This may help to better understand diabetes-induced liver pathologies and potentially provide target to develop efficient therapies. Methods: Diabetes was induced by a single intraperitoneal (ip) injection of STZ (65 mg/kg). Inflammatory status in the rat liver was determined in the fourth week after diabetes induction by measuring expression of pro-inflammatory cytokines (TNFα, IL- 6) and related production of anti-inflammatory protein haptoglobin (Hp). We also studied the effects of HMGB1 on inflammation through its interaction with TLR4 and related downstream signaling pathways in terms of inhibited HMGB1 secretion in diabetic rats by ethyl pyruvate (EP) treatment (80 mg/kg/ip/daily). Results: The results show that decrease in eHMGB1 expression caused by EP treatment, correlates with reduced level of TNFα, IL-6 and Hp in the serum and liver of diabetic rats. These changes are in accordance with significant decrease in HMGB1/TLR4 interaction and decreased activation of MAPK (p38, ERK, JNK), NF-κB p65 and JAK1/STAT3 signaling pathways in diabetic liver. Conclusion: In diabetic liver eHMGB1 is involved in the inflammatory response dually. It acts pro-inflammatory by enhancing production of inflammatory mediators and anti-inflammatory by increasing Hp expression.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats
SP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5246
ER  - 

@conference{
author = "Jovanović Stojanov, Sofija and Grigorov, Ilijana and Petrović, Anja and Bogojević, Desanka and Ivanović Matić, Svetlana and Martinović, Vesna",
year = "2017",
abstract = "Introduction: Oxidative stress and chronic low-grade inflammation in diabetes leads to liver injury. During diabetes, extracellular level of high-mobility group box-1 (HMGB1) protein increases. Considering that extracellular HMGB1 (eHMGB1) protein functions as an pro-inflammatory mediator, triggering inflammatory responses by promoting the expression of inflammatory cytokines, the aim of this study was to investigate its contribution to the maintenance of inflammatory condition in the liver of diabetic rats. This may help to better understand diabetes-induced liver pathologies and potentially provide target to develop efficient therapies. Methods: Diabetes was induced by a single intraperitoneal (ip) injection of STZ (65 mg/kg). Inflammatory status in the rat liver was determined in the fourth week after diabetes induction by measuring expression of pro-inflammatory cytokines (TNFα, IL- 6) and related production of anti-inflammatory protein haptoglobin (Hp). We also studied the effects of HMGB1 on inflammation through its interaction with TLR4 and related downstream signaling pathways in terms of inhibited HMGB1 secretion in diabetic rats by ethyl pyruvate (EP) treatment (80 mg/kg/ip/daily). Results: The results show that decrease in eHMGB1 expression caused by EP treatment, correlates with reduced level of TNFα, IL-6 and Hp in the serum and liver of diabetic rats. These changes are in accordance with significant decrease in HMGB1/TLR4 interaction and decreased activation of MAPK (p38, ERK, JNK), NF-κB p65 and JAK1/STAT3 signaling pathways in diabetic liver. Conclusion: In diabetic liver eHMGB1 is involved in the inflammatory response dually. It acts pro-inflammatory by enhancing production of inflammatory mediators and anti-inflammatory by increasing Hp expression.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5246"
}

Jovanović Stojanov, S., Grigorov, I., Petrović, A., Bogojević, D., Ivanović Matić, S.,& Martinović, V.. (2017). Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 44.
https://hdl.handle.net/21.15107/rcub_ibiss_5246

Jovanović Stojanov S, Grigorov I, Petrović A, Bogojević D, Ivanović Matić S, Martinović V. Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:44.
https://hdl.handle.net/21.15107/rcub_ibiss_5246 .

Jovanović Stojanov, Sofija, Grigorov, Ilijana, Petrović, Anja, Bogojević, Desanka, Ivanović Matić, Svetlana, Martinović, Vesna, "Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):44,
https://hdl.handle.net/21.15107/rcub_ibiss_5246 .

TY  - CONF
AU  - Petrović, Anja
AU  - Ivanović Matić, Svetlana
AU  - Bogojević, Desanka
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović Stojanov, Sofija
AU  - Stevanović, Jelena
AU  - Grigorov, Ilijana
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5244
AB  - Introduction: Hepatocellular death is the main trigger of liver disease. Since diabetic patients are very prone to liver diseases there is a urgent need to identify key regulators of cell death processes. High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein with a role in apoptotic and autophagic activation when it is present in cytosol and extracellular space. The aim of this study was to elucidate HMGB1 contribution to liver injury trough activation of apoptosis and autophagy in streptozotocin (STZ)-induced diabetic rats since the role of HMGB1 in hepatic cell death during diabetes is partially known. Methods: Diabetes was induced with a single intraperitoneal (i.p.) injection of STZ (65 mg/kg). Inhibition of HMGB1 release was achieved by ethyl pyruvate (80 mg/kg/i.p./daily). We followed changes in expression of serum and cytosolic HMGB1 and its interaction with TLR4 and RAGE and how these changes affect on apoptotic and autophagic activity and liver morphology. Results: In the serum of diabetic rats elevated levels of HMGB1 were accompanied by increased HMGB1 interactions with TLR4 and RAGE receptors. Enhancement in these interactions led to increased activity of both apoptotic and autophagic signaling pathways resulting in altered liver morphology and acummulation of autophagosomes in hepatocytes. Inhibition of HMGB1 release caused reduction in apoptotic and autophagic activity which resulted in preservation of normal liver architecture and decreased number of autophagosomes. Conclusion: HMGB1 causes liver damage through activation of apoptosis and autophagy, therefore it’s a suitable new target for prevention of liver diseases in diabetic patients.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats
SP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5244
ER  - 

@conference{
author = "Petrović, Anja and Ivanović Matić, Svetlana and Bogojević, Desanka and Martinović, Vesna and Korać, Aleksandra and Jovanović Stojanov, Sofija and Stevanović, Jelena and Grigorov, Ilijana",
year = "2017",
abstract = "Introduction: Hepatocellular death is the main trigger of liver disease. Since diabetic patients are very prone to liver diseases there is a urgent need to identify key regulators of cell death processes. High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein with a role in apoptotic and autophagic activation when it is present in cytosol and extracellular space. The aim of this study was to elucidate HMGB1 contribution to liver injury trough activation of apoptosis and autophagy in streptozotocin (STZ)-induced diabetic rats since the role of HMGB1 in hepatic cell death during diabetes is partially known. Methods: Diabetes was induced with a single intraperitoneal (i.p.) injection of STZ (65 mg/kg). Inhibition of HMGB1 release was achieved by ethyl pyruvate (80 mg/kg/i.p./daily). We followed changes in expression of serum and cytosolic HMGB1 and its interaction with TLR4 and RAGE and how these changes affect on apoptotic and autophagic activity and liver morphology. Results: In the serum of diabetic rats elevated levels of HMGB1 were accompanied by increased HMGB1 interactions with TLR4 and RAGE receptors. Enhancement in these interactions led to increased activity of both apoptotic and autophagic signaling pathways resulting in altered liver morphology and acummulation of autophagosomes in hepatocytes. Inhibition of HMGB1 release caused reduction in apoptotic and autophagic activity which resulted in preservation of normal liver architecture and decreased number of autophagosomes. Conclusion: HMGB1 causes liver damage through activation of apoptosis and autophagy, therefore it’s a suitable new target for prevention of liver diseases in diabetic patients.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats",
pages = "65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5244"
}

Petrović, A., Ivanović Matić, S., Bogojević, D., Martinović, V., Korać, A., Jovanović Stojanov, S., Stevanović, J.,& Grigorov, I.. (2017). Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 65.
https://hdl.handle.net/21.15107/rcub_ibiss_5244

Petrović A, Ivanović Matić S, Bogojević D, Martinović V, Korać A, Jovanović Stojanov S, Stevanović J, Grigorov I. Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:65.
https://hdl.handle.net/21.15107/rcub_ibiss_5244 .

Petrović, Anja, Ivanović Matić, Svetlana, Bogojević, Desanka, Martinović, Vesna, Korać, Aleksandra, Jovanović Stojanov, Sofija, Stevanović, Jelena, Grigorov, Ilijana, "Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):65,
https://hdl.handle.net/21.15107/rcub_ibiss_5244 .

TY  - CONF
AU  - Martinović, Vesna
AU  - Jovanović Stojanov, Sofija
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Petrović, Anja
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5245
AB  - Introduction: Oxidative stress and inflammation are involved in the pathogenesis of diabetes. Previously, we showed that melatonin exerts potent anti-oxidative and anti-inflammatory actions in the liver of streptozotocin (STZ)-induced diabetic rats, thus correcting diabetes-associated abnormalities. The concept of a liver-spleen axis has been proposed as an intersection linking immunity and metabolism in various conditions, including chronic liver diseases. We therefore compared the effect of melatonin on oxidative stress and the inflammatory response in the liver and spleen of STZ-induced diabetic rats. Methods: Male Wistar rats were injected with 65 mg/kg STZ to induce diabetes. Melatonin was administrated daily (0.2 mg/kg/i.p) until the end of the study at 4 weeks after diabetes induction. Oxidative stress was assessed by measuring the level of lipid peroxidation and the changes in antioxidative enzyme activities. Inflammation was evaluated by examining the levels of proinflammatory cytokines, inflammatory mediators and the acute-phase protein haptoglobin (Hp). Results: In both tissues, melatonin lowered oxidative stress, which was observed as a decrease in lipid peroxidation and increased expression and activity of CAT, MnSOD and CuZnSOD. By suppressing the activation of NF-κB p65 and MAPK (p38, JNK, ERK) signaling cascades and by decreasing the production of TNF-α, IL-6, HMGB1 and Hp, melatonin also reduced inflammation. Conclusion: Melatonin stimulated the antioxidative defense in both, the spleen and liver of diabetic rats and attenuated inflammation via the same molecular mechanisms.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats
SP  - 55
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5245
ER  - 

@conference{
author = "Martinović, Vesna and Jovanović Stojanov, Sofija and Bogojević, Desanka and Ivanović Matić, Svetlana and Petrović, Anja and Poznanović, Goran and Grigorov, Ilijana",
year = "2017",
abstract = "Introduction: Oxidative stress and inflammation are involved in the pathogenesis of diabetes. Previously, we showed that melatonin exerts potent anti-oxidative and anti-inflammatory actions in the liver of streptozotocin (STZ)-induced diabetic rats, thus correcting diabetes-associated abnormalities. The concept of a liver-spleen axis has been proposed as an intersection linking immunity and metabolism in various conditions, including chronic liver diseases. We therefore compared the effect of melatonin on oxidative stress and the inflammatory response in the liver and spleen of STZ-induced diabetic rats. Methods: Male Wistar rats were injected with 65 mg/kg STZ to induce diabetes. Melatonin was administrated daily (0.2 mg/kg/i.p) until the end of the study at 4 weeks after diabetes induction. Oxidative stress was assessed by measuring the level of lipid peroxidation and the changes in antioxidative enzyme activities. Inflammation was evaluated by examining the levels of proinflammatory cytokines, inflammatory mediators and the acute-phase protein haptoglobin (Hp). Results: In both tissues, melatonin lowered oxidative stress, which was observed as a decrease in lipid peroxidation and increased expression and activity of CAT, MnSOD and CuZnSOD. By suppressing the activation of NF-κB p65 and MAPK (p38, JNK, ERK) signaling cascades and by decreasing the production of TNF-α, IL-6, HMGB1 and Hp, melatonin also reduced inflammation. Conclusion: Melatonin stimulated the antioxidative defense in both, the spleen and liver of diabetic rats and attenuated inflammation via the same molecular mechanisms.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats",
pages = "55",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5245"
}

Martinović, V., Jovanović Stojanov, S., Bogojević, D., Ivanović Matić, S., Petrović, A., Poznanović, G.,& Grigorov, I.. (2017). Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 55.
https://hdl.handle.net/21.15107/rcub_ibiss_5245

Martinović V, Jovanović Stojanov S, Bogojević D, Ivanović Matić S, Petrović A, Poznanović G, Grigorov I. Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:55.
https://hdl.handle.net/21.15107/rcub_ibiss_5245 .

Martinović, Vesna, Jovanović Stojanov, Sofija, Bogojević, Desanka, Ivanović Matić, Svetlana, Petrović, Anja, Poznanović, Goran, Grigorov, Ilijana, "Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):55,
https://hdl.handle.net/21.15107/rcub_ibiss_5245 .

TY  - JOUR
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Korać, Aleksandra
AU  - Golić, Igor
AU  - Jovanović Stojanov, Sofija
AU  - Martinović, Vesna
AU  - Ivanović Matić, Svetlana
AU  - Stevanović, Jelena
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2017
UR  - http://link.springer.com/10.1007/s13105-017-0574-0
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28695466
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2787
AB  - The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.
T2  - Journal of Physiology and Biochemistry
T1  - Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.
DO  - 10.1007/s13105-017-0574-0
ER  - 

@article{
author = "Petrović, Anja and Bogojević, Desanka and Korać, Aleksandra and Golić, Igor and Jovanović Stojanov, Sofija and Martinović, Vesna and Ivanović Matić, Svetlana and Stevanović, Jelena and Poznanović, Goran and Grigorov, Ilijana",
year = "2017",
abstract = "The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.",
journal = "Journal of Physiology and Biochemistry",
title = "Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.",
doi = "10.1007/s13105-017-0574-0"
}

Petrović, A., Bogojević, D., Korać, A., Golić, I., Jovanović Stojanov, S., Martinović, V., Ivanović Matić, S., Stevanović, J., Poznanović, G.,& Grigorov, I.. (2017). Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.. in Journal of Physiology and Biochemistry.
https://doi.org/10.1007/s13105-017-0574-0

Petrović A, Bogojević D, Korać A, Golić I, Jovanović Stojanov S, Martinović V, Ivanović Matić S, Stevanović J, Poznanović G, Grigorov I. Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.. in Journal of Physiology and Biochemistry. 2017;.
doi:10.1007/s13105-017-0574-0 .

Petrović, Anja, Bogojević, Desanka, Korać, Aleksandra, Golić, Igor, Jovanović Stojanov, Sofija, Martinović, Vesna, Ivanović Matić, Svetlana, Stevanović, Jelena, Poznanović, Goran, Grigorov, Ilijana, "Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver." in Journal of Physiology and Biochemistry (2017),
https://doi.org/10.1007/s13105-017-0574-0 . .

TY  - THES
AU  - Petrović, Anja
PY  - 2017
UR  - http://uvidok.rcub.bg.ac.rs/handle/123456789/2142
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2851
AB  - Ćelijska smrt je jedan od uzroka patoloških promena u jetri tokom dijabetesa. Protein koji može imati važnu ulogu u ovim procesima, bilo kao marker nekroze ili aktivator signalnih puteva koji vode ćelijskoj smrti ili preživljavanju, je HMGB1. U vanćelijsku sredinu HMGB1 dospeva iz nekrotičnih, oštećenih ćelija i aktiviranih imunskih ćelija. U ovoj doktorskoj disertaciji ispitivana je uloga ovog proteina u određivanju profila ćelijske smrti u jetri pacova sa dijabetesom kroz njegov doprinos u modulaciji procesa apoptoze i autofagije. Rezultati ovog istraživanja pokazali su da je nivo HMGB1 proteina u serumu i jetri pacova sa dijabetesom u korelaciji sa nivoom oštećenja jetre i nekroze, što ga svrstava među potencijalne biološke markere za praćenje dijabetičnih komplikacija u jetri. Na aktivaciju procesa apoptoze i autofagije HMGB1 protein deluje dvojako, kroz aktivaciju nizvodnih signalnih puteva pokrenutih interakcijama vanćelijskog HMGB1 sa TLR4 i RAGE receptorima, i kroz uticaj citoplazmatskog HMGB1 na formiranje autofagozoma kroz interakcije sa Beklinom1. Pokazano je da nivo vanćelijskog HMGB1 proteina i njegov doprinos profilu ćelijske smrti u jetri zavisi od intenziteta prisutnog oksidativnog stresa. U uslovima oksidativnog stresa prisutnog u nelečenom dijabetesu, HMGB1 favorizuje puteve apoptoze i doprinosi ćelijskoj smrti i oštećenju jetre. Smanjenjem oksidativnog stresa i nivoa vanćelijskog HMGB1 melatoninom ili etil piruvatom, favorizuje se delovanje citoplazmatskog HMGB1 u pravcu protektivne autofagije i uklanjanja oštećenih unutarćelijskih struktura. Ovi podaci ukazuju na terapeutski značaj melatonina i etil piruvata u regulaciji aktivnosti HMGB1 u dijabetesu i na ulogu HMGB1 proteina u regulaciji i povezivanju apoptoze i autofagije.
AB  - Cell death underlies hepatic pathological changes in diabetes. HMGB1 is a protein with important roles in these changes, whether as a necrotic marker or a pathway activator determining cell death or survival. HMGB1 is released into the extracellular space by damaged or necrotic cells and activated immune cells. The role of HMGB1 in determining the profile of cell death in the liver of diabetic rats was studied by examining its role in the modulation of apoptosis and autophagy. The levels of HMGB1 protein in the serum and liver of diabetic rats correlate with the degree of necrosis and liver damage, thus rendering HMGB1 as a potential biological marker of diabetic complications. To activate apoptosis and autophagy, HMGB1 protein acts by stimulating downstream signaling pathways triggered by interactions of extracellular HMGB1 with TLR4 and RAGE receptors, and through the activity of cytoplasmic HMGB1 on the formation of autophagosomes via interaction with Beclin1, which has a central role in autophagy. Extracellular expression of HMGB1 and its contribution to the cell death profile in the liver depends on the level of oxidative stress. In oxidative stress accompanying untreated diabetes, HMGB1 promotes apoptosis and resulting liver damage. The reduction of oxidative stress by melatonin and HMGB1 release by ethyl pyruvate stimulates the cytoprotective role of cytosolic HMGB1 in autophagy activation These results points to the therapeutic significance of melatonin and ethyl pyruvate in the regulation of HMGB1 activity in diabetes, and the role of HMGB1 in the regulation and interplay between apoptosis and autophagy.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Uloga HMGB1 proteina u modifikaciji i integraciji signalnih puteva apoptoze i autofagije u ćelijama jetre pacova sa indukovanim dijabetesom
T1  - The role of HMGB1 protein in the modification and integration of apoptosis and autophagy signaling pathways in liver cells of diabetic rats
SP  - 1
EP  - 161
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2851
ER  - 

@phdthesis{
author = "Petrović, Anja",
year = "2017",
abstract = "Ćelijska smrt je jedan od uzroka patoloških promena u jetri tokom dijabetesa. Protein koji može imati važnu ulogu u ovim procesima, bilo kao marker nekroze ili aktivator signalnih puteva koji vode ćelijskoj smrti ili preživljavanju, je HMGB1. U vanćelijsku sredinu HMGB1 dospeva iz nekrotičnih, oštećenih ćelija i aktiviranih imunskih ćelija. U ovoj doktorskoj disertaciji ispitivana je uloga ovog proteina u određivanju profila ćelijske smrti u jetri pacova sa dijabetesom kroz njegov doprinos u modulaciji procesa apoptoze i autofagije. Rezultati ovog istraživanja pokazali su da je nivo HMGB1 proteina u serumu i jetri pacova sa dijabetesom u korelaciji sa nivoom oštećenja jetre i nekroze, što ga svrstava među potencijalne biološke markere za praćenje dijabetičnih komplikacija u jetri. Na aktivaciju procesa apoptoze i autofagije HMGB1 protein deluje dvojako, kroz aktivaciju nizvodnih signalnih puteva pokrenutih interakcijama vanćelijskog HMGB1 sa TLR4 i RAGE receptorima, i kroz uticaj citoplazmatskog HMGB1 na formiranje autofagozoma kroz interakcije sa Beklinom1. Pokazano je da nivo vanćelijskog HMGB1 proteina i njegov doprinos profilu ćelijske smrti u jetri zavisi od intenziteta prisutnog oksidativnog stresa. U uslovima oksidativnog stresa prisutnog u nelečenom dijabetesu, HMGB1 favorizuje puteve apoptoze i doprinosi ćelijskoj smrti i oštećenju jetre. Smanjenjem oksidativnog stresa i nivoa vanćelijskog HMGB1 melatoninom ili etil piruvatom, favorizuje se delovanje citoplazmatskog HMGB1 u pravcu protektivne autofagije i uklanjanja oštećenih unutarćelijskih struktura. Ovi podaci ukazuju na terapeutski značaj melatonina i etil piruvata u regulaciji aktivnosti HMGB1 u dijabetesu i na ulogu HMGB1 proteina u regulaciji i povezivanju apoptoze i autofagije., Cell death underlies hepatic pathological changes in diabetes. HMGB1 is a protein with important roles in these changes, whether as a necrotic marker or a pathway activator determining cell death or survival. HMGB1 is released into the extracellular space by damaged or necrotic cells and activated immune cells. The role of HMGB1 in determining the profile of cell death in the liver of diabetic rats was studied by examining its role in the modulation of apoptosis and autophagy. The levels of HMGB1 protein in the serum and liver of diabetic rats correlate with the degree of necrosis and liver damage, thus rendering HMGB1 as a potential biological marker of diabetic complications. To activate apoptosis and autophagy, HMGB1 protein acts by stimulating downstream signaling pathways triggered by interactions of extracellular HMGB1 with TLR4 and RAGE receptors, and through the activity of cytoplasmic HMGB1 on the formation of autophagosomes via interaction with Beclin1, which has a central role in autophagy. Extracellular expression of HMGB1 and its contribution to the cell death profile in the liver depends on the level of oxidative stress. In oxidative stress accompanying untreated diabetes, HMGB1 promotes apoptosis and resulting liver damage. The reduction of oxidative stress by melatonin and HMGB1 release by ethyl pyruvate stimulates the cytoprotective role of cytosolic HMGB1 in autophagy activation These results points to the therapeutic significance of melatonin and ethyl pyruvate in the regulation of HMGB1 activity in diabetes, and the role of HMGB1 in the regulation and interplay between apoptosis and autophagy.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Uloga HMGB1 proteina u modifikaciji i integraciji signalnih puteva apoptoze i autofagije u ćelijama jetre pacova sa indukovanim dijabetesom, The role of HMGB1 protein in the modification and integration of apoptosis and autophagy signaling pathways in liver cells of diabetic rats",
pages = "1-161",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2851"
}

Petrović, A.. (2017). Uloga HMGB1 proteina u modifikaciji i integraciji signalnih puteva apoptoze i autofagije u ćelijama jetre pacova sa indukovanim dijabetesom. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-161.
https://hdl.handle.net/21.15107/rcub_ibiss_2851

Petrović A. Uloga HMGB1 proteina u modifikaciji i integraciji signalnih puteva apoptoze i autofagije u ćelijama jetre pacova sa indukovanim dijabetesom. in University of Belgrade, Faculty of Biology. 2017;:1-161.
https://hdl.handle.net/21.15107/rcub_ibiss_2851 .

Petrović, Anja, "Uloga HMGB1 proteina u modifikaciji i integraciji signalnih puteva apoptoze i autofagije u ćelijama jetre pacova sa indukovanim dijabetesom" in University of Belgrade, Faculty of Biology (2017):1-161,
https://hdl.handle.net/21.15107/rcub_ibiss_2851 .

TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Martinović, Vesna
AU  - Jovanović Stojanov, Sofija
AU  - Stevanović, Jelena
AU  - Blagojević, Duško
AU  - Grigorov, Ilijana
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4280
AB  - Melatonin, a hormone secreted primarly by pineal gland,exhibitsantioxidative and anti-inflammatory properties. We have previously reported antinecrotic effect of melatonin in the liver of streptozotocin (STZ) treated rats. However, molecular mechanisms underlyingmelatonin hepatoprotective rolein oxidative enviroment are still partially known. In this study we investigated effects of melatonin on the role of nuclear factor-kappa B (NF-κB) p65 and nuclear erythroid 2-related factor 2 (Nrf2) in the liver of STZ treated rats.Melatonin at doses of 2 mg/kg/i.p was administrated daily, 3 days before STZ treatment (65mg/kg, i.p), and continued until the end of study at 4 weeks after STZ injection. STZ treatment causeshypoinsulinemia followed by hyperglycemia which increases the production of reactive oxidative species (ROS) leading tooxidative stress. ROS activatedNF-κB p65 in hepatocytes and increased its nuclear expresssion where it enhances expression of genes of proinflammatory cytokines leading to elevated presence of TNFα and IL-6. High TNFα has a cytotoxic activity and may potentiate liver damage.Melatonin reduced the elevated expression of NF-κB p65, TNFα and IL-6.STZ treatmentincreased expression of Nrf2 but reduced its activation which is followed by decrease in superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) expression and activity. Melatonin significantly increases nuclear expression of Nrf2 which enhances the up-regulation of SOD, GST and CAT expression and activity.The results of this study suggest that melatonin improves oxidative–induced liver damage by attenuation of proinflammatory stimuli through decreasing of NF-κB activation cascade and strengthens antioxidative defence through activation of Nrf2 cascade.
PB  - Bratislava: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences
C3  - 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts
T1  - Melatonin attenuates streptozotocin induced inflammation and oxidative stress in the rat liver by modulation of NF-kB and Nrf2 signaling
SP  - 39
EP  - 39
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4280
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović Matić, Svetlana and Martinović, Vesna and Jovanović Stojanov, Sofija and Stevanović, Jelena and Blagojević, Duško and Grigorov, Ilijana",
year = "2016",
abstract = "Melatonin, a hormone secreted primarly by pineal gland,exhibitsantioxidative and anti-inflammatory properties. We have previously reported antinecrotic effect of melatonin in the liver of streptozotocin (STZ) treated rats. However, molecular mechanisms underlyingmelatonin hepatoprotective rolein oxidative enviroment are still partially known. In this study we investigated effects of melatonin on the role of nuclear factor-kappa B (NF-κB) p65 and nuclear erythroid 2-related factor 2 (Nrf2) in the liver of STZ treated rats.Melatonin at doses of 2 mg/kg/i.p was administrated daily, 3 days before STZ treatment (65mg/kg, i.p), and continued until the end of study at 4 weeks after STZ injection. STZ treatment causeshypoinsulinemia followed by hyperglycemia which increases the production of reactive oxidative species (ROS) leading tooxidative stress. ROS activatedNF-κB p65 in hepatocytes and increased its nuclear expresssion where it enhances expression of genes of proinflammatory cytokines leading to elevated presence of TNFα and IL-6. High TNFα has a cytotoxic activity and may potentiate liver damage.Melatonin reduced the elevated expression of NF-κB p65, TNFα and IL-6.STZ treatmentincreased expression of Nrf2 but reduced its activation which is followed by decrease in superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) expression and activity. Melatonin significantly increases nuclear expression of Nrf2 which enhances the up-regulation of SOD, GST and CAT expression and activity.The results of this study suggest that melatonin improves oxidative–induced liver damage by attenuation of proinflammatory stimuli through decreasing of NF-κB activation cascade and strengthens antioxidative defence through activation of Nrf2 cascade.",
publisher = "Bratislava: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences",
journal = "2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts",
title = "Melatonin attenuates streptozotocin induced inflammation and oxidative stress in the rat liver by modulation of NF-kB and Nrf2 signaling",
pages = "39-39",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4280"
}

Petrović, A., Bogojević, D., Ivanović Matić, S., Martinović, V., Jovanović Stojanov, S., Stevanović, J., Blagojević, D.,& Grigorov, I.. (2016). Melatonin attenuates streptozotocin induced inflammation and oxidative stress in the rat liver by modulation of NF-kB and Nrf2 signaling. in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts
Bratislava: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences., 39-39.
https://hdl.handle.net/21.15107/rcub_ibiss_4280

Petrović A, Bogojević D, Ivanović Matić S, Martinović V, Jovanović Stojanov S, Stevanović J, Blagojević D, Grigorov I. Melatonin attenuates streptozotocin induced inflammation and oxidative stress in the rat liver by modulation of NF-kB and Nrf2 signaling. in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts. 2016;:39-39.
https://hdl.handle.net/21.15107/rcub_ibiss_4280 .

Petrović, Anja, Bogojević, Desanka, Ivanović Matić, Svetlana, Martinović, Vesna, Jovanović Stojanov, Sofija, Stevanović, Jelena, Blagojević, Duško, Grigorov, Ilijana, "Melatonin attenuates streptozotocin induced inflammation and oxidative stress in the rat liver by modulation of NF-kB and Nrf2 signaling" in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts (2016):39-39,
https://hdl.handle.net/21.15107/rcub_ibiss_4280 .

TY  - CONF
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Mileusnić, Dina
AU  - Grigorov, Ilijana
AU  - Petrović, Anja
AU  - Zolotarevski, Lidija
AU  - Nikolic, Milica
AU  - Kataranovski, Milena
PY  - 2015
UR  - http://www.medf.kg.ac.rs/efis/Arandjelovac%20Abstract%20book%202015.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4811
AB  - Gastrointestinal (GI) tract is one of the main targets of cadmium (Cd),
important food and drinking water contaminant. In this study, the effect of
subchronic (30 days) oral (in drinking water) intake of environmentally
relevant doses of cadmium (5µg/ml and 50µg/ml) on intestinal [(tissue of
duodenum and mesenteric lymph node (mLN) cells)] was examined in
Dark Agouti (DA) rats. Atomic absorption spectrophotometry (AAS)
analysis revealed significant cadmium load in duodenum,which was
associated with changes of both intestinal bacterial load and composition
(Denaturing Gradient Gel Electrophoresis/DGGE).Shortening of villi,
damage to epithelium, increases in goblet-like vacuoles and mononuclear
cell infiltration in lamina propria were histologically evident at both
cadmium doses, with massive necrosis at higher Cd dose (judging by High
Mobility Group Box-1/HMGB-1 Western blot analysis).Increased levels of
proinflammatory cytokines (IL-1β, IFN-γ, IL-17) were observed at both Cd
doses (TNFα at higher dose solely). Cadmium administration affected
draining lymph nodes as well, judging by signs of stress response (drop of
cellular reduced glutathione/GSH at higher dose, rise of
metallothionein/MT mRNA at both doses).Increased cellularity of mLN
was observed at higher Cd dose, but with no changes in proliferative
responses. Intake of both Cd doses resulted in higher (compared to controls)
levels of IFN-γ and IL-17 mRNA as well as increased mLN cell
responsiveness to ConA stimulation.Significant increases in numbers of
CD68+ cells and stimulation of innate immune activities (numbers of
dihydrorhodamine/DHR+ cells and intracellular myeloperoxidase/MPO+
cells, LPS-stimulated nitric oxide/NO production and ex vivo IL-1β
expression) were observed at higher dose of cadmium.Proinflammatory
effects of cadmium might have resulted from changes in gut microbiota and
tissue damage.Interactions of this metal with intestinal immune system
should be taken into account when assessing dietary cadmium as health risk
factor.
PB  - Belgrade: Immunological Society of Serbia
C3  - 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia
T1  - Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats
SP  - 48
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4811
ER  - 

@conference{
editor = "Lukić, Miodrag, Jonjic, Stipan, Nikolich-Zugich, Janko",
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Mirkov, Ivana and Mileusnić, Dina and Grigorov, Ilijana and Petrović, Anja and Zolotarevski, Lidija and Nikolic, Milica and Kataranovski, Milena",
year = "2015",
abstract = "Gastrointestinal (GI) tract is one of the main targets of cadmium (Cd),
important food and drinking water contaminant. In this study, the effect of
subchronic (30 days) oral (in drinking water) intake of environmentally
relevant doses of cadmium (5µg/ml and 50µg/ml) on intestinal [(tissue of
duodenum and mesenteric lymph node (mLN) cells)] was examined in
Dark Agouti (DA) rats. Atomic absorption spectrophotometry (AAS)
analysis revealed significant cadmium load in duodenum,which was
associated with changes of both intestinal bacterial load and composition
(Denaturing Gradient Gel Electrophoresis/DGGE).Shortening of villi,
damage to epithelium, increases in goblet-like vacuoles and mononuclear
cell infiltration in lamina propria were histologically evident at both
cadmium doses, with massive necrosis at higher Cd dose (judging by High
Mobility Group Box-1/HMGB-1 Western blot analysis).Increased levels of
proinflammatory cytokines (IL-1β, IFN-γ, IL-17) were observed at both Cd
doses (TNFα at higher dose solely). Cadmium administration affected
draining lymph nodes as well, judging by signs of stress response (drop of
cellular reduced glutathione/GSH at higher dose, rise of
metallothionein/MT mRNA at both doses).Increased cellularity of mLN
was observed at higher Cd dose, but with no changes in proliferative
responses. Intake of both Cd doses resulted in higher (compared to controls)
levels of IFN-γ and IL-17 mRNA as well as increased mLN cell
responsiveness to ConA stimulation.Significant increases in numbers of
CD68+ cells and stimulation of innate immune activities (numbers of
dihydrorhodamine/DHR+ cells and intracellular myeloperoxidase/MPO+
cells, LPS-stimulated nitric oxide/NO production and ex vivo IL-1β
expression) were observed at higher dose of cadmium.Proinflammatory
effects of cadmium might have resulted from changes in gut microbiota and
tissue damage.Interactions of this metal with intestinal immune system
should be taken into account when assessing dietary cadmium as health risk
factor.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia",
title = "Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats",
pages = "48",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4811"
}

Lukić, M., Jonjic, S., Nikolich-Zugich, J., Ninkov, M., Popov Aleksandrov, A., Demenesku, J., Mirkov, I., Mileusnić, D., Grigorov, I., Petrović, A., Zolotarevski, L., Nikolic, M.,& Kataranovski, M.. (2015). Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats. in 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia
Belgrade: Immunological Society of Serbia., 48.
https://hdl.handle.net/21.15107/rcub_ibiss_4811

Lukić M, Jonjic S, Nikolich-Zugich J, Ninkov M, Popov Aleksandrov A, Demenesku J, Mirkov I, Mileusnić D, Grigorov I, Petrović A, Zolotarevski L, Nikolic M, Kataranovski M. Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats. in 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia. 2015;:48.
https://hdl.handle.net/21.15107/rcub_ibiss_4811 .

Lukić, Miodrag, Jonjic, Stipan, Nikolich-Zugich, Janko, Ninkov, Marina, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Mirkov, Ivana, Mileusnić, Dina, Grigorov, Ilijana, Petrović, Anja, Zolotarevski, Lidija, Nikolic, Milica, Kataranovski, Milena, "Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats" in 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia (2015):48,
https://hdl.handle.net/21.15107/rcub_ibiss_4811 .

TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović-Matić, Svetlana
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović-Stojanov, Sofija
AU  - Stevanović, Jelena
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5654
AB  - Autophagy is a cellular process that involves lysosomal degradation and recycling of intracellular
organelles and proteins. By removing damaged and dysfunctional cellular components in order to
maintain energy homeostasis during cellular stress, autophagy can serve as a cytoprotective
mechanism. Also, it could lead to cell death if it‟s overactive or defective. Molecular mechanisms
responsible for the two faces of autophagy are still partially known. Therefore, for the development of
therapy based on autophagy modulation, it‟s necessary to fully define these processes. This study
investigated the role of oxidative stress on autophagic processes in the liver of diabetic rats and effects
of melatonin, as an antioxidant, on autophagy initiation/modulation. The liver, as one of the main
target organs of insulin, takes an important role in regulation of glucose homeostasis. In diabetes,
hypoinsulinemia followed by hyperglycemia increases mitochondrial proton gradient within the cells.
In this state organelles become the source of reactive oxidative species leading to macromolecule
damage which may cause necrotic, apoptotic or autophagic cell death. In the liver of diabetic rats
obtained four weeks after diabetes induction with streptozotocin (65 mg/kg, i.p.), light and electron
transmission microscopy showed significant changes in the structure of the cells and a large number of
necrotic cells. By using Western blot, immunoprecipitation and confocal microscopy analyses,
autophagy in diabetic liver was confirmed by increased expression of proteins required for
autophagosome formation, LC3B and Beclin1, and by the presence of Beclin1 interactions with its
activator HMGB1. In the state of oxidative stress HMGB1 is relocated from the nucleus to the
cytoplasm. Continuous melatonin treatment of diabetic rats (2mg/kg/daily, i.p.) leads to significant
reduction of liver damage, presumably through elevated mitochondrial autophagy. Melatonin
additionally contributes to elevated expression of LC3B and Beclin1, HMGB1-Beclin1 interactions
and autophagosome formation. Thus, it seems that melatonin protects the liver from diabetes induced
damage by favoring autophagy as a protective mechanism.
PB  - Belgrade : Serbian Society for Mitochondrial and Free-Radical Physiology
C3  - Book of Abstracts: Third Congress Redox Medicine: Reactive Species Signaling, Analytical Methods, Phytopharmacy, Molecular Mechanisms of Disease - SSMFRP-2015; 2015 Sep 25-26; Belgrade, Serbia
T1  - Effects of melatonin on autophagic processes in the liver of diabetic rats
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5654
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović-Matić, Svetlana and Martinović, Vesna and Korać, Aleksandra and Jovanović-Stojanov, Sofija and Stevanović, Jelena and Poznanović, Goran and Grigorov, Ilijana",
year = "2015",
abstract = "Autophagy is a cellular process that involves lysosomal degradation and recycling of intracellular
organelles and proteins. By removing damaged and dysfunctional cellular components in order to
maintain energy homeostasis during cellular stress, autophagy can serve as a cytoprotective
mechanism. Also, it could lead to cell death if it‟s overactive or defective. Molecular mechanisms
responsible for the two faces of autophagy are still partially known. Therefore, for the development of
therapy based on autophagy modulation, it‟s necessary to fully define these processes. This study
investigated the role of oxidative stress on autophagic processes in the liver of diabetic rats and effects
of melatonin, as an antioxidant, on autophagy initiation/modulation. The liver, as one of the main
target organs of insulin, takes an important role in regulation of glucose homeostasis. In diabetes,
hypoinsulinemia followed by hyperglycemia increases mitochondrial proton gradient within the cells.
In this state organelles become the source of reactive oxidative species leading to macromolecule
damage which may cause necrotic, apoptotic or autophagic cell death. In the liver of diabetic rats
obtained four weeks after diabetes induction with streptozotocin (65 mg/kg, i.p.), light and electron
transmission microscopy showed significant changes in the structure of the cells and a large number of
necrotic cells. By using Western blot, immunoprecipitation and confocal microscopy analyses,
autophagy in diabetic liver was confirmed by increased expression of proteins required for
autophagosome formation, LC3B and Beclin1, and by the presence of Beclin1 interactions with its
activator HMGB1. In the state of oxidative stress HMGB1 is relocated from the nucleus to the
cytoplasm. Continuous melatonin treatment of diabetic rats (2mg/kg/daily, i.p.) leads to significant
reduction of liver damage, presumably through elevated mitochondrial autophagy. Melatonin
additionally contributes to elevated expression of LC3B and Beclin1, HMGB1-Beclin1 interactions
and autophagosome formation. Thus, it seems that melatonin protects the liver from diabetes induced
damage by favoring autophagy as a protective mechanism.",
publisher = "Belgrade : Serbian Society for Mitochondrial and Free-Radical Physiology",
journal = "Book of Abstracts: Third Congress Redox Medicine: Reactive Species Signaling, Analytical Methods, Phytopharmacy, Molecular Mechanisms of Disease - SSMFRP-2015; 2015 Sep 25-26; Belgrade, Serbia",
title = "Effects of melatonin on autophagic processes in the liver of diabetic rats",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5654"
}

Petrović, A., Bogojević, D., Ivanović-Matić, S., Martinović, V., Korać, A., Jovanović-Stojanov, S., Stevanović, J., Poznanović, G.,& Grigorov, I.. (2015). Effects of melatonin on autophagic processes in the liver of diabetic rats. in Book of Abstracts: Third Congress Redox Medicine: Reactive Species Signaling, Analytical Methods, Phytopharmacy, Molecular Mechanisms of Disease - SSMFRP-2015; 2015 Sep 25-26; Belgrade, Serbia
Belgrade : Serbian Society for Mitochondrial and Free-Radical Physiology., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_5654

Petrović A, Bogojević D, Ivanović-Matić S, Martinović V, Korać A, Jovanović-Stojanov S, Stevanović J, Poznanović G, Grigorov I. Effects of melatonin on autophagic processes in the liver of diabetic rats. in Book of Abstracts: Third Congress Redox Medicine: Reactive Species Signaling, Analytical Methods, Phytopharmacy, Molecular Mechanisms of Disease - SSMFRP-2015; 2015 Sep 25-26; Belgrade, Serbia. 2015;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_5654 .

Petrović, Anja, Bogojević, Desanka, Ivanović-Matić, Svetlana, Martinović, Vesna, Korać, Aleksandra, Jovanović-Stojanov, Sofija, Stevanović, Jelena, Poznanović, Goran, Grigorov, Ilijana, "Effects of melatonin on autophagic processes in the liver of diabetic rats" in Book of Abstracts: Third Congress Redox Medicine: Reactive Species Signaling, Analytical Methods, Phytopharmacy, Molecular Mechanisms of Disease - SSMFRP-2015; 2015 Sep 25-26; Belgrade, Serbia (2015):33,
https://hdl.handle.net/21.15107/rcub_ibiss_5654 .

TY  - JOUR
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jovanović Stojanov, Sofija
AU  - Petrović, Anja
AU  - Ivanović Matić, Svetlana
AU  - Zolotarevski, Lidija
AU  - Poznanović, Goran
AU  - Martinović, Vesna
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2210
AB  - Oxidative stress-mediated damage to liver tissue underlies the
   pathological alterations in liver morphology and function that are
   observed in diabetes. We examined the effects of the antioxidant action
   of melatonin against necrosis-inducing DNA damage in hepatocytes of
   streptozotocin (STZ)-induced diabetic rats. Daily administration of
   melatonin (0.2 mg/kg) was initiated 3 days before diabetes induction and
   maintained for 4 weeks. Melatonin-treated diabetic rats exhibited
   improved markers of liver injury (P<0.05), alkaline phosphatase, and
   alanine and aspartate aminotransferases. Melatonin prevented the
   diabetes-related morphological deterioration of hepatocytes, DNA damage
   (P<0.05), and hepatocellular necrosis. The improvement was due to
   containment of the pronecrotic oxygen radical load, observed as
   inhibition (P<0.05) of the diabetes-induced rise in lipid peroxidation
   and hydrogen peroxide increase in the liver. This was accompanied by
   improved necrotic markers of cellular damage: a significant reduction in
   cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1)
   into necrotic 55- and 62-kDa fragments, and inhibition of
   nucleus-to-cytoplasm translocation and accumulation in the serum of the
   high-mobility group box 1 (HMGB1) protein. We conclude that melatonin is
   hepatoprotective in diabetes. It reduces extensive DNA damage and
   resulting necrotic processes. Melatonin application could thus present a
   viable therapeutic option in the management of diabetes-induced liver
   injury.
T2  - Journal of Physiology and Biochemistry
T1  - Hepatoprotective effects of melatonin against pronecrotic cellular
 events in streptozotocin-induced diabetic rats
IS  - 2
VL  - 70
DO  - 10.1007/s13105-014-0322-7
SP  - 441
EP  - 450
ER  - 

@article{
author = "Grigorov, Ilijana and Bogojević, Desanka and Jovanović Stojanov, Sofija and Petrović, Anja and Ivanović Matić, Svetlana and Zolotarevski, Lidija and Poznanović, Goran and Martinović, Vesna",
year = "2014",
abstract = "Oxidative stress-mediated damage to liver tissue underlies the
   pathological alterations in liver morphology and function that are
   observed in diabetes. We examined the effects of the antioxidant action
   of melatonin against necrosis-inducing DNA damage in hepatocytes of
   streptozotocin (STZ)-induced diabetic rats. Daily administration of
   melatonin (0.2 mg/kg) was initiated 3 days before diabetes induction and
   maintained for 4 weeks. Melatonin-treated diabetic rats exhibited
   improved markers of liver injury (P<0.05), alkaline phosphatase, and
   alanine and aspartate aminotransferases. Melatonin prevented the
   diabetes-related morphological deterioration of hepatocytes, DNA damage
   (P<0.05), and hepatocellular necrosis. The improvement was due to
   containment of the pronecrotic oxygen radical load, observed as
   inhibition (P<0.05) of the diabetes-induced rise in lipid peroxidation
   and hydrogen peroxide increase in the liver. This was accompanied by
   improved necrotic markers of cellular damage: a significant reduction in
   cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1)
   into necrotic 55- and 62-kDa fragments, and inhibition of
   nucleus-to-cytoplasm translocation and accumulation in the serum of the
   high-mobility group box 1 (HMGB1) protein. We conclude that melatonin is
   hepatoprotective in diabetes. It reduces extensive DNA damage and
   resulting necrotic processes. Melatonin application could thus present a
   viable therapeutic option in the management of diabetes-induced liver
   injury.",
journal = "Journal of Physiology and Biochemistry",
title = "Hepatoprotective effects of melatonin against pronecrotic cellular
 events in streptozotocin-induced diabetic rats",
number = "2",
volume = "70",
doi = "10.1007/s13105-014-0322-7",
pages = "441-450"
}

Grigorov, I., Bogojević, D., Jovanović Stojanov, S., Petrović, A., Ivanović Matić, S., Zolotarevski, L., Poznanović, G.,& Martinović, V.. (2014). Hepatoprotective effects of melatonin against pronecrotic cellular
 events in streptozotocin-induced diabetic rats. in Journal of Physiology and Biochemistry, 70(2), 441-450.
https://doi.org/10.1007/s13105-014-0322-7

Grigorov I, Bogojević D, Jovanović Stojanov S, Petrović A, Ivanović Matić S, Zolotarevski L, Poznanović G, Martinović V. Hepatoprotective effects of melatonin against pronecrotic cellular
 events in streptozotocin-induced diabetic rats. in Journal of Physiology and Biochemistry. 2014;70(2):441-450.
doi:10.1007/s13105-014-0322-7 .

Grigorov, Ilijana, Bogojević, Desanka, Jovanović Stojanov, Sofija, Petrović, Anja, Ivanović Matić, Svetlana, Zolotarevski, Lidija, Poznanović, Goran, Martinović, Vesna, "Hepatoprotective effects of melatonin against pronecrotic cellular
 events in streptozotocin-induced diabetic rats" in Journal of Physiology and Biochemistry, 70, no. 2 (2014):441-450,
https://doi.org/10.1007/s13105-014-0322-7 . .

TY  - CONF
AU  - Petrović, Anja
AU  - Martinović, Vesna
AU  - Bogojević, Desanka
AU  - Jovanović Stojanov, Sofija
AU  - Ivanović-Matić, Svetlana
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5430
AB  - Dijabetes predstavlja metabolički poremećaj koji je okarakterisan hiperglikemijom i sa njom udruženim oksidativnim stresom koji dovodi do oštećenja i disfunkcije mnogih organa. Patološke promene morfologije i funkcije jetre tokom razvoja dijabetesa glavni su uzroci različitih bolesti jetre. Kod dijabetičnih pacijenata dolazi do promena u veličini jetre kao rezultat izmenjenog broja ćelija usled njihovog rasta ili ćelijske smrti. U osnovi üelijske smrti putem nekroze nalaze se DNK oštećenja. Obzirom da tokom dijabetesa dolazi do smanjenja nivoa melatonina, u ovom radu ispitivan je antioksidativni uticaj dnevnog unosa melatonina na stepen DNK oštećenja i prisustvo nekrotskih promena u ćelijama jetre pacova kod kojih je dijabetes izazvan jednokratnim injeciranjem streptozotocina u dozi od 65 mg/kg. Eksperiment su činile kontrolna grupa pacova soja Wistar, grupa koja je primala melatonin (0.2 mg/kg), grupa sa dijabetesom i grupa dijabetičnih pacova tretiranih melatoninom. Tretman melatoninom počeo je tri dana pre injeciranja streptozotocina i trajao je četiri nedelje. Stepen oksidativnog stresa praćen je određivanjem lipidnog statusa i merenjem koncentracije vodonik peroksida (H2O2) u cirkulaciji i jetri. Oštećenje jetre je utvrđivano histološki i preko serumskog nivoa alanin aminotransferaze, aspartat aminotransferaze i alkalne fosfataze. Oštećenja DNK ispitivana su Komet analizom. Prisustvo nekrotskih promena praćeno je histološki i imunoblot analizom profila sečenja DNK reparacionog enzima, PARP-1 (engl. Poly(ADP-ribose)polymerase-1) i subćelijske lokalizacije i ekstraćelijskog prisustva signalnog proteina nekroze, HMGB1 (engl. High Mobility Group Box 1). Dijabetični pacovi tretirani melatoninom ispoljavali su značajno niži nivo oksidativnog stresa i oštećenja jetre u odnosu na dijabetične. Melatonin je očuvao strukturu jetre dijabetičnih pacova i značajno smanjio nivo hidropsne degeneracije i broj nekrotičnih ćelija što korelira sa smanjenjem DNK oštećenja za 77%, redukovanom pojavom nekrotskih fragmenata PARP-1 (55kDa i 62 kDa) i zadržavanjem HMGB1 proteina u jedru. Zaključeno je da melatonin svojim antioksidativnim delovanjem štiti jetru od oštećenja uzrokovanih dijabetičnim stanjem i da bi mogao biti od koristi kao vid terapije kod obolelih od dijabetesa.
PB  - Beograd: Srpsko društvo za mitohondrijalnu i slobodno-radikalsku fiziologiju
PB  - Beograd: Ministarstvo prosvete, nauke i tehnološkog razvoja
PB  - Beograd: Biološki fakultet
PB  - Niš: Medicinski fakultet
C3  - Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia
T1  - Antinekrotski efekat melatonina u jetri dijabetičnih pacova
SP  - 35
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5430
ER  - 

@conference{
author = "Petrović, Anja and Martinović, Vesna and Bogojević, Desanka and Jovanović Stojanov, Sofija and Ivanović-Matić, Svetlana and Poznanović, Goran and Grigorov, Ilijana",
year = "2013",
abstract = "Dijabetes predstavlja metabolički poremećaj koji je okarakterisan hiperglikemijom i sa njom udruženim oksidativnim stresom koji dovodi do oštećenja i disfunkcije mnogih organa. Patološke promene morfologije i funkcije jetre tokom razvoja dijabetesa glavni su uzroci različitih bolesti jetre. Kod dijabetičnih pacijenata dolazi do promena u veličini jetre kao rezultat izmenjenog broja ćelija usled njihovog rasta ili ćelijske smrti. U osnovi üelijske smrti putem nekroze nalaze se DNK oštećenja. Obzirom da tokom dijabetesa dolazi do smanjenja nivoa melatonina, u ovom radu ispitivan je antioksidativni uticaj dnevnog unosa melatonina na stepen DNK oštećenja i prisustvo nekrotskih promena u ćelijama jetre pacova kod kojih je dijabetes izazvan jednokratnim injeciranjem streptozotocina u dozi od 65 mg/kg. Eksperiment su činile kontrolna grupa pacova soja Wistar, grupa koja je primala melatonin (0.2 mg/kg), grupa sa dijabetesom i grupa dijabetičnih pacova tretiranih melatoninom. Tretman melatoninom počeo je tri dana pre injeciranja streptozotocina i trajao je četiri nedelje. Stepen oksidativnog stresa praćen je određivanjem lipidnog statusa i merenjem koncentracije vodonik peroksida (H2O2) u cirkulaciji i jetri. Oštećenje jetre je utvrđivano histološki i preko serumskog nivoa alanin aminotransferaze, aspartat aminotransferaze i alkalne fosfataze. Oštećenja DNK ispitivana su Komet analizom. Prisustvo nekrotskih promena praćeno je histološki i imunoblot analizom profila sečenja DNK reparacionog enzima, PARP-1 (engl. Poly(ADP-ribose)polymerase-1) i subćelijske lokalizacije i ekstraćelijskog prisustva signalnog proteina nekroze, HMGB1 (engl. High Mobility Group Box 1). Dijabetični pacovi tretirani melatoninom ispoljavali su značajno niži nivo oksidativnog stresa i oštećenja jetre u odnosu na dijabetične. Melatonin je očuvao strukturu jetre dijabetičnih pacova i značajno smanjio nivo hidropsne degeneracije i broj nekrotičnih ćelija što korelira sa smanjenjem DNK oštećenja za 77%, redukovanom pojavom nekrotskih fragmenata PARP-1 (55kDa i 62 kDa) i zadržavanjem HMGB1 proteina u jedru. Zaključeno je da melatonin svojim antioksidativnim delovanjem štiti jetru od oštećenja uzrokovanih dijabetičnim stanjem i da bi mogao biti od koristi kao vid terapije kod obolelih od dijabetesa.",
publisher = "Beograd: Srpsko društvo za mitohondrijalnu i slobodno-radikalsku fiziologiju, Beograd: Ministarstvo prosvete, nauke i tehnološkog razvoja, Beograd: Biološki fakultet, Niš: Medicinski fakultet",
journal = "Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia",
title = "Antinekrotski efekat melatonina u jetri dijabetičnih pacova",
pages = "35",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5430"
}

Petrović, A., Martinović, V., Bogojević, D., Jovanović Stojanov, S., Ivanović-Matić, S., Poznanović, G.,& Grigorov, I.. (2013). Antinekrotski efekat melatonina u jetri dijabetičnih pacova. in Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia
Beograd: Srpsko društvo za mitohondrijalnu i slobodno-radikalsku fiziologiju., 35.
https://hdl.handle.net/21.15107/rcub_ibiss_5430

Petrović A, Martinović V, Bogojević D, Jovanović Stojanov S, Ivanović-Matić S, Poznanović G, Grigorov I. Antinekrotski efekat melatonina u jetri dijabetičnih pacova. in Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia. 2013;:35.
https://hdl.handle.net/21.15107/rcub_ibiss_5430 .

Petrović, Anja, Martinović, Vesna, Bogojević, Desanka, Jovanović Stojanov, Sofija, Ivanović-Matić, Svetlana, Poznanović, Goran, Grigorov, Ilijana, "Antinekrotski efekat melatonina u jetri dijabetičnih pacova" in Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia (2013):35,
https://hdl.handle.net/21.15107/rcub_ibiss_5430 .

TY  - CONF
AU  - Petrović, Anja
AU  - Ivanović-Matić, Svetlana
AU  - Bogojević, Desanka
AU  - Martinović, Vesna
AU  - Jovanović-Stojanov, Sofija
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5651
AB  - Oxidative stress-related cardiomyocyte damage in diabetes represents a major risk factor for heart disease. Reactive oxygen species triggers a series of deleterious stimuli that result in protein and DNA damage, cell dysfunction and cell death. Our previous study showed that the absence of cardiomyopathy in rats with streptozotocin (STZ)-induced diabetes is accompanied with significantly higher antioxidative activity of catalase (CAT), suggesting that CAT may be one of the key enzymes in heart protection during diabetes. To confirm this hypothesis we analysed oxidative status and extent of DNA damage in cardiomyocytes of diabetic rats with inhibited CAT activity. Diabetes was induced by intraperitoneal (i.p.) injection of ST2 at 40 mg/kg/day for five consecutive days. Inhibition of CAT activity was established by daily i.p. administration of 1 mg/kg 3-amino-1,2,4 triazole throughout the 4 week period, starting from the 15th day of STZ administration. Increased lipid per-oxidation and H2O2, concentration in the heart of diabetic rats with inhibited CAT activity indicated higher level of oxidative stress when compared with diabetic ones. This is followed with decline of glutathione level, activity of glutathione peroxidase and total superoxide dismutase and increased activity of manganese superoxide dismutase whose overexpression could potentiate cardiac CAT activity. According to comet assay, impairment in antioxidant defense system led to significantly increased DNA damage in cardiomyocytes of rats with inhibited CAT activity in comparison with cardiomyocytes of diabetic rats. Also, Western immunoblot revealed that inhibition of CAT activity in diabetic heart was followed by twofold decrease in CAT expression as a result of the decrease in expression of Nrf2, the main transcription factor involved in CAT gene induction. These results suggest that. CAT expression and activity is crucial in prevention of heart damage during diabetes.
PB  - Heidelberg, Germany: EMBL
C3  - Abstracts presented at the 15th international EMBL PhD Symposium: Competition in Biology: The race for survival from molecules to systems; 2013 Nov 21-23; Heidelberg, Germany
T1  - Catalase prevents cardiomyocyte DNA damage during diabetes
SP  - 55
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5651
ER  - 

@conference{
author = "Petrović, Anja and Ivanović-Matić, Svetlana and Bogojević, Desanka and Martinović, Vesna and Jovanović-Stojanov, Sofija and Poznanović, Goran and Grigorov, Ilijana",
year = "2013",
abstract = "Oxidative stress-related cardiomyocyte damage in diabetes represents a major risk factor for heart disease. Reactive oxygen species triggers a series of deleterious stimuli that result in protein and DNA damage, cell dysfunction and cell death. Our previous study showed that the absence of cardiomyopathy in rats with streptozotocin (STZ)-induced diabetes is accompanied with significantly higher antioxidative activity of catalase (CAT), suggesting that CAT may be one of the key enzymes in heart protection during diabetes. To confirm this hypothesis we analysed oxidative status and extent of DNA damage in cardiomyocytes of diabetic rats with inhibited CAT activity. Diabetes was induced by intraperitoneal (i.p.) injection of ST2 at 40 mg/kg/day for five consecutive days. Inhibition of CAT activity was established by daily i.p. administration of 1 mg/kg 3-amino-1,2,4 triazole throughout the 4 week period, starting from the 15th day of STZ administration. Increased lipid per-oxidation and H2O2, concentration in the heart of diabetic rats with inhibited CAT activity indicated higher level of oxidative stress when compared with diabetic ones. This is followed with decline of glutathione level, activity of glutathione peroxidase and total superoxide dismutase and increased activity of manganese superoxide dismutase whose overexpression could potentiate cardiac CAT activity. According to comet assay, impairment in antioxidant defense system led to significantly increased DNA damage in cardiomyocytes of rats with inhibited CAT activity in comparison with cardiomyocytes of diabetic rats. Also, Western immunoblot revealed that inhibition of CAT activity in diabetic heart was followed by twofold decrease in CAT expression as a result of the decrease in expression of Nrf2, the main transcription factor involved in CAT gene induction. These results suggest that. CAT expression and activity is crucial in prevention of heart damage during diabetes.",
publisher = "Heidelberg, Germany: EMBL",
journal = "Abstracts presented at the 15th international EMBL PhD Symposium: Competition in Biology: The race for survival from molecules to systems; 2013 Nov 21-23; Heidelberg, Germany",
title = "Catalase prevents cardiomyocyte DNA damage during diabetes",
pages = "55",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5651"
}

Petrović, A., Ivanović-Matić, S., Bogojević, D., Martinović, V., Jovanović-Stojanov, S., Poznanović, G.,& Grigorov, I.. (2013). Catalase prevents cardiomyocyte DNA damage during diabetes. in Abstracts presented at the 15th international EMBL PhD Symposium: Competition in Biology: The race for survival from molecules to systems; 2013 Nov 21-23; Heidelberg, Germany
Heidelberg, Germany: EMBL., 55.
https://hdl.handle.net/21.15107/rcub_ibiss_5651

Petrović A, Ivanović-Matić S, Bogojević D, Martinović V, Jovanović-Stojanov S, Poznanović G, Grigorov I. Catalase prevents cardiomyocyte DNA damage during diabetes. in Abstracts presented at the 15th international EMBL PhD Symposium: Competition in Biology: The race for survival from molecules to systems; 2013 Nov 21-23; Heidelberg, Germany. 2013;:55.
https://hdl.handle.net/21.15107/rcub_ibiss_5651 .

Petrović, Anja, Ivanović-Matić, Svetlana, Bogojević, Desanka, Martinović, Vesna, Jovanović-Stojanov, Sofija, Poznanović, Goran, Grigorov, Ilijana, "Catalase prevents cardiomyocyte DNA damage during diabetes" in Abstracts presented at the 15th international EMBL PhD Symposium: Competition in Biology: The race for survival from molecules to systems; 2013 Nov 21-23; Heidelberg, Germany (2013):55,
https://hdl.handle.net/21.15107/rcub_ibiss_5651 .

TY  - CONF
AU  - Jovanović Stojanov, Sofija
AU  - Martinović, Vesna
AU  - Bogojević, Desanka
AU  - Ivanović-Matić, Svetlana
AU  - Petrović, Anja
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5429
AB  - Hipoinsulinemija i hiperglikemija koje nastaju tokom dijabetesa, uzrokuju pojavu metaboličkog i oksidativnog stresa koji dovode do stanja hronične inflamacije, progresivne disfunkcije i oštećenja jetre. Za predikciju i prevenciju pojave dijabetičnih komplikacija u jetri od interesa je identifikacija endogenih molekula koji svojim delovanjem doprinose njenom oštećenju. U tom smislu izdvaja se protein HMGB1. Prvobitno okarakterisan kao DNK- vezujući protein sa ulogom u organizaciji hromatinske strukture, HMGB1 može biti prisutan u ekstraćelijskom miljeu gde ima ulogu proinflamatornog citokina i medijatora tkivnih oštećenja. U vanćelijsku sredinu HMGB1 dospeva pasivno iz nekroznih ili oštećenih ćelija ili regulisanom sekrecijom iz ćelija izloženih stresu. U ovom radu ispitivan je uticaj oksidativnog statusa na subćelijsku lokalizaciju i ukupno prisustvo HMGB1 proteina u jetri i serumu pacova sa dijabetesom tipa I i promene nastale nakon tretmana dijabetičnih pacova sa antioksidansom melatoninom.
Dijabetes tipa I uspostavljen je davanjem jednokratne doze streptozotocina (65 mg/kg) pacovima soja Wistar. Tretman kontrolnih i dijabetičnih pacova melatoninom (0.2 mg/kg) započet je tri dana pre indukcije dijabetesa i vršen je svakodnevno tokom 4   nedelje.
Dijabetično stanje karakteriše značajan porast koncentracije vodonik peroksida (H2O2), i superoksid anjon radikala (O .-) u serumu, porast lipidne peroksidacije i pad aktivnosti antioksidativnih enzima katalaze, superoksid dismutaza i glutation S transferaze u serumu i
jetri. Ovakav oksidativni status prati značajni porast koncentracije alanin aminotransferaze (ALT), pokazatelja oštećenja jetre, za oko 3.2 puta kao i značajan porast nivoa HMGB1 proteina (2.1 put) u serumu i ukupnim homogenatima jetre (2.3 puta). Imunohistohemijski utvrđena je prevashodno citoplazmatska lokalizacija HMGB1 proteina tokom dijabetesa. Bolji oksidativni status uspostavljen tretmanom sa melatoninom dovodi do smanjenja ošteüenja jetre što je praćeno značajnim smanjenjem nivoa HMGB1 proteina u serumu i jetri i njegovim zadržavanjem u jedru ćelija jetre.
Dobijeni rezultati ukazuju da prisustvo HMGB1 proteina u serumu korelira sa stepenom oksidativnog stresa i oštećenjem jetre što navodi na zaključak da HMGB1 protein može biti potencijalni prognostički indikator tkivnih oštećenja kao i meta terapeutskog delovanja kojim bi se menjala njegova lokalizovanost i aktivnost, a time i redukovala disfunkcija jetre tokom dijabetesa.
PB  - Beograd: Srpsko društvo za mitohondrijalnu i slobodno-radikalsku fiziologiju
PB  - Beograd: Ministarstvo prosvete, nauke i tehnološkog razvoja
PB  - Beograd: Biološki fakultet
PB  - Niš: Medicinski fakultet
C3  - Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia
T1  - HMGB1 kao indikator oštećenja jetre uzrokovanog oksidativnim stresom tokom dijabetesa
SP  - 79
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5429
ER  - 

@conference{
author = "Jovanović Stojanov, Sofija and Martinović, Vesna and Bogojević, Desanka and Ivanović-Matić, Svetlana and Petrović, Anja and Poznanović, Goran and Grigorov, Ilijana",
year = "2013",
abstract = "Hipoinsulinemija i hiperglikemija koje nastaju tokom dijabetesa, uzrokuju pojavu metaboličkog i oksidativnog stresa koji dovode do stanja hronične inflamacije, progresivne disfunkcije i oštećenja jetre. Za predikciju i prevenciju pojave dijabetičnih komplikacija u jetri od interesa je identifikacija endogenih molekula koji svojim delovanjem doprinose njenom oštećenju. U tom smislu izdvaja se protein HMGB1. Prvobitno okarakterisan kao DNK- vezujući protein sa ulogom u organizaciji hromatinske strukture, HMGB1 može biti prisutan u ekstraćelijskom miljeu gde ima ulogu proinflamatornog citokina i medijatora tkivnih oštećenja. U vanćelijsku sredinu HMGB1 dospeva pasivno iz nekroznih ili oštećenih ćelija ili regulisanom sekrecijom iz ćelija izloženih stresu. U ovom radu ispitivan je uticaj oksidativnog statusa na subćelijsku lokalizaciju i ukupno prisustvo HMGB1 proteina u jetri i serumu pacova sa dijabetesom tipa I i promene nastale nakon tretmana dijabetičnih pacova sa antioksidansom melatoninom.
Dijabetes tipa I uspostavljen je davanjem jednokratne doze streptozotocina (65 mg/kg) pacovima soja Wistar. Tretman kontrolnih i dijabetičnih pacova melatoninom (0.2 mg/kg) započet je tri dana pre indukcije dijabetesa i vršen je svakodnevno tokom 4   nedelje.
Dijabetično stanje karakteriše značajan porast koncentracije vodonik peroksida (H2O2), i superoksid anjon radikala (O .-) u serumu, porast lipidne peroksidacije i pad aktivnosti antioksidativnih enzima katalaze, superoksid dismutaza i glutation S transferaze u serumu i
jetri. Ovakav oksidativni status prati značajni porast koncentracije alanin aminotransferaze (ALT), pokazatelja oštećenja jetre, za oko 3.2 puta kao i značajan porast nivoa HMGB1 proteina (2.1 put) u serumu i ukupnim homogenatima jetre (2.3 puta). Imunohistohemijski utvrđena je prevashodno citoplazmatska lokalizacija HMGB1 proteina tokom dijabetesa. Bolji oksidativni status uspostavljen tretmanom sa melatoninom dovodi do smanjenja ošteüenja jetre što je praćeno značajnim smanjenjem nivoa HMGB1 proteina u serumu i jetri i njegovim zadržavanjem u jedru ćelija jetre.
Dobijeni rezultati ukazuju da prisustvo HMGB1 proteina u serumu korelira sa stepenom oksidativnog stresa i oštećenjem jetre što navodi na zaključak da HMGB1 protein može biti potencijalni prognostički indikator tkivnih oštećenja kao i meta terapeutskog delovanja kojim bi se menjala njegova lokalizovanost i aktivnost, a time i redukovala disfunkcija jetre tokom dijabetesa.",
publisher = "Beograd: Srpsko društvo za mitohondrijalnu i slobodno-radikalsku fiziologiju, Beograd: Ministarstvo prosvete, nauke i tehnološkog razvoja, Beograd: Biološki fakultet, Niš: Medicinski fakultet",
journal = "Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia",
title = "HMGB1 kao indikator oštećenja jetre uzrokovanog oksidativnim stresom tokom dijabetesa",
pages = "79",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5429"
}

Jovanović Stojanov, S., Martinović, V., Bogojević, D., Ivanović-Matić, S., Petrović, A., Poznanović, G.,& Grigorov, I.. (2013). HMGB1 kao indikator oštećenja jetre uzrokovanog oksidativnim stresom tokom dijabetesa. in Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia
Beograd: Srpsko društvo za mitohondrijalnu i slobodno-radikalsku fiziologiju., 79.
https://hdl.handle.net/21.15107/rcub_ibiss_5429

Jovanović Stojanov S, Martinović V, Bogojević D, Ivanović-Matić S, Petrović A, Poznanović G, Grigorov I. HMGB1 kao indikator oštećenja jetre uzrokovanog oksidativnim stresom tokom dijabetesa. in Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia. 2013;:79.
https://hdl.handle.net/21.15107/rcub_ibiss_5429 .

Jovanović Stojanov, Sofija, Martinović, Vesna, Bogojević, Desanka, Ivanović-Matić, Svetlana, Petrović, Anja, Poznanović, Goran, Grigorov, Ilijana, "HMGB1 kao indikator oštećenja jetre uzrokovanog oksidativnim stresom tokom dijabetesa" in Knjiga sažetaka: Drugi kongres Život sa slobodnim radikalima: Hemija, Biologija, Medicina, SDMSRF-2013; 2013 Sep 28; Niš, Serbia (2013):79,
https://hdl.handle.net/21.15107/rcub_ibiss_5429 .

TY  - JOUR
AU  - Martinović, Vesna
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Petrović, Anja
AU  - Jovanović Stojanov, Sofija
AU  - Ilić, Mirka
AU  - Ivanović-Matić, Svetlana
PY  - 2012
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6069
AB  - Aims: Diabetes-related oxidative stress conditions lead to progressive tissue damage and
disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not
fully understood. The aim of this study was to find relationship between diabetes-related
DNA damage in the rat liver and activities of prosurvival signaling pathways. Methods:
Diabetes, induced by single intraperitoneal injection of streptozotocin, was analyzed two
(development stage) and eight weeks after treatment (stable diabetes). Extent of DNA
damage, analysed by commet assay, was corelated with oxidative status (plasma level of
ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1,
JNK, JAK) and transcription factors NF-kB p65 and STAT3. Results: Significant DNA
damage in development stage is accompanied by elevated plasma levels of O2
- and H2O2,
decreased activities of CAT, MnSOD, and GST in the liver and increased activation of
proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is
accompanied by elevated plasma level of O2
-, restored antioxidative liver enzyme
activity, decreased activation of JNK and increased activation of prosurvival Akt and
ERK signal pathways. Conclusion: These findings indicate that level of DNA damage in
diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance
between JNK and Akt/ERK signal pathways activation.
PB  - Karger Publishers
T2  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
T1  - Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats
IS  - 3
VL  - 30
DO  - 10.1159/000341452
SP  - 723
EP  - 734
ER  - 

@article{
author = "Martinović, Vesna and Grigorov, Ilijana and Bogojević, Desanka and Petrović, Anja and Jovanović Stojanov, Sofija and Ilić, Mirka and Ivanović-Matić, Svetlana",
year = "2012",
abstract = "Aims: Diabetes-related oxidative stress conditions lead to progressive tissue damage and
disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not
fully understood. The aim of this study was to find relationship between diabetes-related
DNA damage in the rat liver and activities of prosurvival signaling pathways. Methods:
Diabetes, induced by single intraperitoneal injection of streptozotocin, was analyzed two
(development stage) and eight weeks after treatment (stable diabetes). Extent of DNA
damage, analysed by commet assay, was corelated with oxidative status (plasma level of
ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1,
JNK, JAK) and transcription factors NF-kB p65 and STAT3. Results: Significant DNA
damage in development stage is accompanied by elevated plasma levels of O2
- and H2O2,
decreased activities of CAT, MnSOD, and GST in the liver and increased activation of
proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is
accompanied by elevated plasma level of O2
-, restored antioxidative liver enzyme
activity, decreased activation of JNK and increased activation of prosurvival Akt and
ERK signal pathways. Conclusion: These findings indicate that level of DNA damage in
diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance
between JNK and Akt/ERK signal pathways activation.",
publisher = "Karger Publishers",
journal = "Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology",
title = "Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats",
number = "3",
volume = "30",
doi = "10.1159/000341452",
pages = "723-734"
}

Martinović, V., Grigorov, I., Bogojević, D., Petrović, A., Jovanović Stojanov, S., Ilić, M.,& Ivanović-Matić, S.. (2012). Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats. in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Karger Publishers., 30(3), 723-734.
https://doi.org/10.1159/000341452

Martinović V, Grigorov I, Bogojević D, Petrović A, Jovanović Stojanov S, Ilić M, Ivanović-Matić S. Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats. in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2012;30(3):723-734.
doi:10.1159/000341452 .

Martinović, Vesna, Grigorov, Ilijana, Bogojević, Desanka, Petrović, Anja, Jovanović Stojanov, Sofija, Ilić, Mirka, Ivanović-Matić, Svetlana, "Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats" in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 30, no. 3 (2012):723-734,
https://doi.org/10.1159/000341452 . .

TY  - JOUR
AU  - Martinović, Vesna
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Petrović, Anja
AU  - Jovanović Stojanov, Sofija
AU  - Ilić, Mirka
AU  - Ivanović Matić, Svetlana
PY  - 2012
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4865
AB  - Aims: Diabetes-related oxidative stress conditions lead to progressive tissue damage and disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not fully understood. The aim of this study was to find relationship between diabetes-related DNA damage in the rat liver and activities of prosurvival signaling pathways.

Methods: Effect of diabetes was analyzed two (development stage) and eight weeks (stable diabetes) after single intraperitoneal injection of streptozotocin. Extent of DNA damage, analysed by comet assay, was corelated with oxidative status (plasma level of ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1, JNK, JAK) and transcription factors NF-κB p65 and STAT3.

Results: Significant DNA damage in development stage is accompanied by elevated plasma levels of O(2)(-) and H(2)O(2), decreased activities of CAT, MnSOD, and GST in the liver and increased activation of proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is accompanied by elevated plasma level of O(2)(-), restored antioxidative liver enzyme activity, decreased activation of JNK and increased activation of prosurvival Akt and ERK signal pathways.

Conclusion: These findings indicate that level of DNA damage in diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance between JNK and Akt/ERK signal pathways activation .
PB  - Basel: Krager
T2  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
T1  - Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats
IS  - 3
VL  - 30
DO  - 10.1159/000341452
SP  - 732
EP  - 734
ER  - 

@article{
author = "Martinović, Vesna and Grigorov, Ilijana and Bogojević, Desanka and Petrović, Anja and Jovanović Stojanov, Sofija and Ilić, Mirka and Ivanović Matić, Svetlana",
year = "2012",
abstract = "Aims: Diabetes-related oxidative stress conditions lead to progressive tissue damage and disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not fully understood. The aim of this study was to find relationship between diabetes-related DNA damage in the rat liver and activities of prosurvival signaling pathways.

Methods: Effect of diabetes was analyzed two (development stage) and eight weeks (stable diabetes) after single intraperitoneal injection of streptozotocin. Extent of DNA damage, analysed by comet assay, was corelated with oxidative status (plasma level of ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1, JNK, JAK) and transcription factors NF-κB p65 and STAT3.

Results: Significant DNA damage in development stage is accompanied by elevated plasma levels of O(2)(-) and H(2)O(2), decreased activities of CAT, MnSOD, and GST in the liver and increased activation of proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is accompanied by elevated plasma level of O(2)(-), restored antioxidative liver enzyme activity, decreased activation of JNK and increased activation of prosurvival Akt and ERK signal pathways.

Conclusion: These findings indicate that level of DNA damage in diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance between JNK and Akt/ERK signal pathways activation .",
publisher = "Basel: Krager",
journal = "Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology",
title = "Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats",
number = "3",
volume = "30",
doi = "10.1159/000341452",
pages = "732-734"
}

Martinović, V., Grigorov, I., Bogojević, D., Petrović, A., Jovanović Stojanov, S., Ilić, M.,& Ivanović Matić, S.. (2012). Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats. in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Basel: Krager., 30(3), 732-734.
https://doi.org/10.1159/000341452

Martinović V, Grigorov I, Bogojević D, Petrović A, Jovanović Stojanov S, Ilić M, Ivanović Matić S. Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats. in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2012;30(3):732-734.
doi:10.1159/000341452 .

Martinović, Vesna, Grigorov, Ilijana, Bogojević, Desanka, Petrović, Anja, Jovanović Stojanov, Sofija, Ilić, Mirka, Ivanović Matić, Svetlana, "Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats" in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 30, no. 3 (2012):732-734,
https://doi.org/10.1159/000341452 . .