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  - 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  - JOUR
AU  - Milić, Ljiljana
AU  - Grigorov, Ilijana
AU  - Krstić, Slobodan
AU  - Ćeranić, Miljan S.
AU  - Jovanović, Bojan
AU  - Stevanović, Jelena
AU  - Peško, Predrag
PY  - 2017
UR  - http://www.degruyter.com/view/j/jomb.2017.36.issue-1/jomb-2016-0016/jomb-2016-0016.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2558
AB  - Background: Intra-abdominal infection in secondary peritonitis drives as excessive production of inflammatory mediators and the development of systemic inflammatory response syndrome (SIRS) or sepsis. Finding a specific marker to distinguish SIRS from sepsis would be of immense clinical importance for the therapeutic approach. It is assumed that high-mobility group box 1 protein (HMGB1) could be such a marker. In this study, we examined the time course changes in the blood levels of HMGB1, C-reactive protein (CRP), procalcitonin (PCT) and serum amyloid A (SAA) in patients with secondary peritonitis who developed SIRS or sepsis.

Methods: In our study, we evaluated 100 patients with diffuse secondary peritonitis who developed SIRS or sepsis (SIRS and SEPSIS group) and 30 patients with inguinal hernia as a control group. Serum levels of HMGB1, CRP, PCT, and SAA were determined on admission in all the patients, and monitored daily in patients with peritonitis until discharge from hospital.

Results: Preoperative HMGB1, CRP, PCT and SAA levels were statistically highly significantly increased in patients with peritonitis compared to patients with inguinal hernia, and significantly higher in patients with sepsis compared to those with SIRS. All four inflammatory markers changed significantly during the follow-up. It is interesting that the patterns of change of HMGB1 and SAA over time were distinctive for SIRS and SEPSIS groups.

Conclusions: HMGB1 and SAA temporal patterns might be useful in distinguishing sepsis from noninfectious SIRS in secondary peritonitis.
T2  - Journal of Medical Biochemistry
T1  - Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status
IS  - 1
VL  - 36
DO  - 10.1515/jomb-2016-0016
SP  - 44
EP  - 53
ER  - 

@article{
author = "Milić, Ljiljana and Grigorov, Ilijana and Krstić, Slobodan and Ćeranić, Miljan S. and Jovanović, Bojan and Stevanović, Jelena and Peško, Predrag",
year = "2017",
abstract = "Background: Intra-abdominal infection in secondary peritonitis drives as excessive production of inflammatory mediators and the development of systemic inflammatory response syndrome (SIRS) or sepsis. Finding a specific marker to distinguish SIRS from sepsis would be of immense clinical importance for the therapeutic approach. It is assumed that high-mobility group box 1 protein (HMGB1) could be such a marker. In this study, we examined the time course changes in the blood levels of HMGB1, C-reactive protein (CRP), procalcitonin (PCT) and serum amyloid A (SAA) in patients with secondary peritonitis who developed SIRS or sepsis.

Methods: In our study, we evaluated 100 patients with diffuse secondary peritonitis who developed SIRS or sepsis (SIRS and SEPSIS group) and 30 patients with inguinal hernia as a control group. Serum levels of HMGB1, CRP, PCT, and SAA were determined on admission in all the patients, and monitored daily in patients with peritonitis until discharge from hospital.

Results: Preoperative HMGB1, CRP, PCT and SAA levels were statistically highly significantly increased in patients with peritonitis compared to patients with inguinal hernia, and significantly higher in patients with sepsis compared to those with SIRS. All four inflammatory markers changed significantly during the follow-up. It is interesting that the patterns of change of HMGB1 and SAA over time were distinctive for SIRS and SEPSIS groups.

Conclusions: HMGB1 and SAA temporal patterns might be useful in distinguishing sepsis from noninfectious SIRS in secondary peritonitis.",
journal = "Journal of Medical Biochemistry",
title = "Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status",
number = "1",
volume = "36",
doi = "10.1515/jomb-2016-0016",
pages = "44-53"
}

Milić, L., Grigorov, I., Krstić, S., Ćeranić, M. S., Jovanović, B., Stevanović, J.,& Peško, P.. (2017). Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status. in Journal of Medical Biochemistry, 36(1), 44-53.
https://doi.org/10.1515/jomb-2016-0016

Milić L, Grigorov I, Krstić S, Ćeranić MS, Jovanović B, Stevanović J, Peško P. Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status. in Journal of Medical Biochemistry. 2017;36(1):44-53.
doi:10.1515/jomb-2016-0016 .

Milić, Ljiljana, Grigorov, Ilijana, Krstić, Slobodan, Ćeranić, Miljan S., Jovanović, Bojan, Stevanović, Jelena, Peško, Predrag, "Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status" in Journal of Medical Biochemistry, 36, no. 1 (2017):44-53,
https://doi.org/10.1515/jomb-2016-0016 . .

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  - 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.
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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 .