TY  - JOUR
AU  - Savić, Nevena
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Grigorov, Ilijana
AU  - Vučetić, Milica
AU  - Martinović, Vesna
AU  - Gudelj, Anđelija
AU  - Otašević, Vesna
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6627
AB  - Recently, we characterized the ferroptotic phenotype in the liver of diabetic
mice and revealed nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2)
inactivation as an integral part of hepatic injury. Here, we aim to investigate
whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes induced hepatic ferroptosis and the mechanisms involved. Male C57BL/6 mice
were divided into four groups: control (vehicle-treated), diabetic (streptozoto cin-induced; 40 mg/kg, from Days 1 to 5), diabetic sulforaphane-treated
(2.5 mg/kg from Days 1 to 42) and non-diabetic sulforaphane-treated group
(2.5 mg/kg from Days 1 to 42). Results showed that diabetes-induced inactiva tion of Nrf2 and decreased expression of its downstream antiferroptotic mole cules critical for antioxidative defense (catalase, superoxide dismutases,
thioredoxin reductase), iron metabolism (ferritin heavy chain (FTH1), ferro portin 1), glutathione (GSH) synthesis (cystine-glutamate antiporter system,
cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine
ligase modifier subunit, glutathione synthetase), and GSH recycling - glutathi one reductase (GR) were reversed/increased by sulforaphane treatment. In
addition, we found that the ferroptotic phenotype in diabetic liver is associated
with increased ferritinophagy and decreased FTH1 immunopositivity. The antiferroptotic effect of sulforaphane was further evidenced through the
increased level of GSH, decreased accumulation of labile iron and lipid perox ides (4-hydroxy-2-nonenal, lipofuscin), decreased ferritinophagy and liver dam age (decreased fibrosis, alanine aminotransferase, and aspartate
aminotransferase). Finally, diabetes-induced increase in serum glucose and tri glyceride level was significantly reduced by sulforaphane. Regardless of the fact
that this study is limited by the use of one model of experimentally induced
diabetes, the results obtained demonstrate for the first time that sulforaphane
prevents diabetes-induced hepatic ferroptosis in vivo through the activation of
Nrf2 signaling pathways. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related
pathologies.
PB  - Hoboken: Wiley
T2  - BioFactors
T1  - Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis
DO  - 10.1002/biof.2042
ER  - 

@article{
author = "Savić, Nevena and Markelić, Milica and Stančić, Ana and Veličković, Ksenija and Grigorov, Ilijana and Vučetić, Milica and Martinović, Vesna and Gudelj, Anđelija and Otašević, Vesna",
year = "2024",
abstract = "Recently, we characterized the ferroptotic phenotype in the liver of diabetic
mice and revealed nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2)
inactivation as an integral part of hepatic injury. Here, we aim to investigate
whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes induced hepatic ferroptosis and the mechanisms involved. Male C57BL/6 mice
were divided into four groups: control (vehicle-treated), diabetic (streptozoto cin-induced; 40 mg/kg, from Days 1 to 5), diabetic sulforaphane-treated
(2.5 mg/kg from Days 1 to 42) and non-diabetic sulforaphane-treated group
(2.5 mg/kg from Days 1 to 42). Results showed that diabetes-induced inactiva tion of Nrf2 and decreased expression of its downstream antiferroptotic mole cules critical for antioxidative defense (catalase, superoxide dismutases,
thioredoxin reductase), iron metabolism (ferritin heavy chain (FTH1), ferro portin 1), glutathione (GSH) synthesis (cystine-glutamate antiporter system,
cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine
ligase modifier subunit, glutathione synthetase), and GSH recycling - glutathi one reductase (GR) were reversed/increased by sulforaphane treatment. In
addition, we found that the ferroptotic phenotype in diabetic liver is associated
with increased ferritinophagy and decreased FTH1 immunopositivity. The antiferroptotic effect of sulforaphane was further evidenced through the
increased level of GSH, decreased accumulation of labile iron and lipid perox ides (4-hydroxy-2-nonenal, lipofuscin), decreased ferritinophagy and liver dam age (decreased fibrosis, alanine aminotransferase, and aspartate
aminotransferase). Finally, diabetes-induced increase in serum glucose and tri glyceride level was significantly reduced by sulforaphane. Regardless of the fact
that this study is limited by the use of one model of experimentally induced
diabetes, the results obtained demonstrate for the first time that sulforaphane
prevents diabetes-induced hepatic ferroptosis in vivo through the activation of
Nrf2 signaling pathways. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related
pathologies.",
publisher = "Hoboken: Wiley",
journal = "BioFactors",
title = "Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis",
doi = "10.1002/biof.2042"
}

Savić, N., Markelić, M., Stančić, A., Veličković, K., Grigorov, I., Vučetić, M., Martinović, V., Gudelj, A.,& Otašević, V.. (2024). Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis. in BioFactors
Hoboken: Wiley..
https://doi.org/10.1002/biof.2042

Savić N, Markelić M, Stančić A, Veličković K, Grigorov I, Vučetić M, Martinović V, Gudelj A, Otašević V. Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis. in BioFactors. 2024;.
doi:10.1002/biof.2042 .

Savić, Nevena, Markelić, Milica, Stančić, Ana, Veličković, Ksenija, Grigorov, Ilijana, Vučetić, Milica, Martinović, Vesna, Gudelj, Anđelija, Otašević, Vesna, "Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis" in BioFactors (2024),
https://doi.org/10.1002/biof.2042 . .

TY  - CONF
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Gudelj, Anđelija
AU  - Savić, Nevena
AU  - Martinović, Vesna
AU  - Grigorov, Ilijana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6403
AB  - A high-sugar diet is associated with an increased risk of chronic intestinal disease1, but the capacity of the gut to adapt to dietary changes in young and adult rats is unknown. Therefore, the effects of an 8-week dextrose-enriched diet (20% or 60%) on intestinal histology, antioxidative defence status, and the expression pattern of high mobility group box-1 (HMGB1), a mediator of the inflammatory response2, were investigated. Numerous signs of tissue damage were associated with decreases in villus height (Vh), crypt depth (Cd), villus surface area (VSA), and muscle thickness (Mt) in adult rats fed with 60% dextrose. While the decrease in Vh and Cd was affected by age, the decrease in VSA and Mt was interactively affected by age and treatment. Structural changes were associated with decreased activity of antioxidative defence enzymes, particularly catalase, which is affected by treatment, and CuZnSOD, which is interactively modulated by age and treatment. Moreover, massive translocation of HMGB1 from the nucleus to the cytoplasm was detected in epithelial cells in the same group (interactive effect of age and treatment). We concluded that supraphysiological dextrose concentrations induce changes in the oxidative state, possibly leading to redox modification of HMGB1 and consequent tissue damage. The intestine undergoes dynamic functional and morphological changes with age that are more pronounced under high dextrose concentrations.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Diet- and age-dependent changes of intestinal injury in rats
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6403
ER  - 

@conference{
author = "Veličković, Ksenija and Markelić, Milica and Stančić, Ana and Otašević, Vesna and Gudelj, Anđelija and Savić, Nevena and Martinović, Vesna and Grigorov, Ilijana",
year = "2023",
abstract = "A high-sugar diet is associated with an increased risk of chronic intestinal disease1, but the capacity of the gut to adapt to dietary changes in young and adult rats is unknown. Therefore, the effects of an 8-week dextrose-enriched diet (20% or 60%) on intestinal histology, antioxidative defence status, and the expression pattern of high mobility group box-1 (HMGB1), a mediator of the inflammatory response2, were investigated. Numerous signs of tissue damage were associated with decreases in villus height (Vh), crypt depth (Cd), villus surface area (VSA), and muscle thickness (Mt) in adult rats fed with 60% dextrose. While the decrease in Vh and Cd was affected by age, the decrease in VSA and Mt was interactively affected by age and treatment. Structural changes were associated with decreased activity of antioxidative defence enzymes, particularly catalase, which is affected by treatment, and CuZnSOD, which is interactively modulated by age and treatment. Moreover, massive translocation of HMGB1 from the nucleus to the cytoplasm was detected in epithelial cells in the same group (interactive effect of age and treatment). We concluded that supraphysiological dextrose concentrations induce changes in the oxidative state, possibly leading to redox modification of HMGB1 and consequent tissue damage. The intestine undergoes dynamic functional and morphological changes with age that are more pronounced under high dextrose concentrations.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Diet- and age-dependent changes of intestinal injury in rats",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6403"
}

Veličković, K., Markelić, M., Stančić, A., Otašević, V., Gudelj, A., Savić, N., Martinović, V.,& Grigorov, I.. (2023). Diet- and age-dependent changes of intestinal injury in rats. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_6403

Veličković K, Markelić M, Stančić A, Otašević V, Gudelj A, Savić N, Martinović V, Grigorov I. Diet- and age-dependent changes of intestinal injury in rats. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_6403 .

Veličković, Ksenija, Markelić, Milica, Stančić, Ana, Otašević, Vesna, Gudelj, Anđelija, Savić, Nevena, Martinović, Vesna, Grigorov, Ilijana, "Diet- and age-dependent changes of intestinal injury in rats" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):80,
https://hdl.handle.net/21.15107/rcub_ibiss_6403 .

TY  - JOUR
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Grigorov, Ilijana
AU  - Mićanović, Dragica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Savić, Nevena
AU  - Gudelj, Anđelija
AU  - Otašević, Vesna
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6071
AB  - Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy
VL  - 14
DO  - 10.3389/fendo.2023.1227498
SP  - 1227498
ER  - 

@article{
author = "Markelić, Milica and Stančić, Ana and Saksida, Tamara and Grigorov, Ilijana and Mićanović, Dragica and Veličković, Ksenija and Martinović, Vesna and Savić, Nevena and Gudelj, Anđelija and Otašević, Vesna",
year = "2023",
abstract = "Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy",
volume = "14",
doi = "10.3389/fendo.2023.1227498",
pages = "1227498"
}

Markelić, M., Stančić, A., Saksida, T., Grigorov, I., Mićanović, D., Veličković, K., Martinović, V., Savić, N., Gudelj, A.,& Otašević, V.. (2023). Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology
Lausanne: Frontiers Media SA., 14, 1227498.
https://doi.org/10.3389/fendo.2023.1227498

Markelić M, Stančić A, Saksida T, Grigorov I, Mićanović D, Veličković K, Martinović V, Savić N, Gudelj A, Otašević V. Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology. 2023;14:1227498.
doi:10.3389/fendo.2023.1227498 .

Markelić, Milica, Stančić, Ana, Saksida, Tamara, Grigorov, Ilijana, Mićanović, Dragica, Veličković, Ksenija, Martinović, Vesna, Savić, Nevena, Gudelj, Anđelija, Otašević, Vesna, "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy" in Frontiers in Endocrinology, 14 (2023):1227498,
https://doi.org/10.3389/fendo.2023.1227498 . .

TY  - CONF
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Markelić, Milica
AU  - Veličković, Ksenija
AU  - Gudelj, Anđelija
AU  - Savić, Nevena
AU  - Martinović, Vesna
AU  - Grigorov, Ilijana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6068
AB  - We showed recently that ferroptosis contributes to liver pathological changes in diabetes. So, targeting of ferroptosis-related pathways could be novel approach for treatment of diabetes- related liver diseases. Ethyl pyruvate (EP) showed antidiabetic action due to anti-oxidative, - inflammatory and -apoptotic properties. We aimed to examine its potential antiferroptotic action  in diabetes-related liver pathology.
Male Wistar rats were divided into four groups: control; diabetic (STZ, 65 mg/kg); diabetic pre- treated with EP (80 mg/kg/day, starting one week before STZ and continuing following 4  weeks) and diabetic treated with EP, starting with STZ and lasted 4   weeks.
Both modes of EP treatment induced attenuation of ferroptotic events in the liver of diabetic  rats: accumulation of lipid peroxides (4-HNE), disturbances in iron metabolism (decreased   FTH and increased TFR expression), decrease in expression level/activity of ferroptosis-  related antioxidative-defense molecules (GPX4, GCL, GSS, Nrf2, HO-1), and activation of ferroptosis-related pro-inflammatory events (HMGB1 nucleus-to-cytosol and NF-kB cytosol-to- nucleus translocation). Those changes reflected on the improvement of diabetes-related morphological alterations such as liver fibrosis and  binucleation.
Overall, EP interferes with ferroptosis signaling pathways and exerts antiferroptotic activity in the liver in diabetic state. This highlighting the significance of ferroptosis targeting in diabetes- related liver diseases and novel mechanisms/targets of EP beneficial   actions.
PB  - EMBO
C3  - EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
T1  - Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate
SP  - 92
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6068
ER  - 

@conference{
author = "Stančić, Ana and Otašević, Vesna and Markelić, Milica and Veličković, Ksenija and Gudelj, Anđelija and Savić, Nevena and Martinović, Vesna and Grigorov, Ilijana",
year = "2023",
abstract = "We showed recently that ferroptosis contributes to liver pathological changes in diabetes. So, targeting of ferroptosis-related pathways could be novel approach for treatment of diabetes- related liver diseases. Ethyl pyruvate (EP) showed antidiabetic action due to anti-oxidative, - inflammatory and -apoptotic properties. We aimed to examine its potential antiferroptotic action  in diabetes-related liver pathology.
Male Wistar rats were divided into four groups: control; diabetic (STZ, 65 mg/kg); diabetic pre- treated with EP (80 mg/kg/day, starting one week before STZ and continuing following 4  weeks) and diabetic treated with EP, starting with STZ and lasted 4   weeks.
Both modes of EP treatment induced attenuation of ferroptotic events in the liver of diabetic  rats: accumulation of lipid peroxides (4-HNE), disturbances in iron metabolism (decreased   FTH and increased TFR expression), decrease in expression level/activity of ferroptosis-  related antioxidative-defense molecules (GPX4, GCL, GSS, Nrf2, HO-1), and activation of ferroptosis-related pro-inflammatory events (HMGB1 nucleus-to-cytosol and NF-kB cytosol-to- nucleus translocation). Those changes reflected on the improvement of diabetes-related morphological alterations such as liver fibrosis and  binucleation.
Overall, EP interferes with ferroptosis signaling pathways and exerts antiferroptotic activity in the liver in diabetic state. This highlighting the significance of ferroptosis targeting in diabetes- related liver diseases and novel mechanisms/targets of EP beneficial   actions.",
publisher = "EMBO",
journal = "EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany",
title = "Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate",
pages = "92",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6068"
}

Stančić, A., Otašević, V., Markelić, M., Veličković, K., Gudelj, A., Savić, N., Martinović, V.,& Grigorov, I.. (2023). Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
EMBO., 92.
https://hdl.handle.net/21.15107/rcub_ibiss_6068

Stančić A, Otašević V, Markelić M, Veličković K, Gudelj A, Savić N, Martinović V, Grigorov I. Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany. 2023;:92.
https://hdl.handle.net/21.15107/rcub_ibiss_6068 .

Stančić, Ana, Otašević, Vesna, Markelić, Milica, Veličković, Ksenija, Gudelj, Anđelija, Savić, Nevena, Martinović, Vesna, Grigorov, Ilijana, "Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate" in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany (2023):92,
https://hdl.handle.net/21.15107/rcub_ibiss_6068 .

TY  - CONF
AU  - Otašević, Vesna
AU  - Grigorov, Ilijana
AU  - Savić, Nevena
AU  - Markelić, Milica
AU  - Veličković, Ksenija
AU  - Gudelj, Anđelija
AU  - Martinović, Vesna
AU  - Stančić, Ana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6067
AB  - Recently, we characterized the ferroptotic phenotype of the liver of diabetic mice and revealed the inactivation of Nrf2 as an integral part of diabetes-induced liver ferroptosis. We aim here to examine does sulforaphane, an Nrf2 activator and antioxidant, prevent diabetes-induced liver ferroptosis and the mechanisms  involved.
For that purpose, male C57BL/6 mice were divided into three groups: control, diabetic (streptozotocin-treated, 40 mg/kg/5 consecutive days), diabetic+sulforaphane treated (2.5 mg/kg, from day 1-42).
Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic parameters crucial for antioxidative defense (HO-1, catalase, SOD), iron metabolism (ferroportin, ferritin), glutathione synthesis (xCT, GCLC, CTH, CBS) and recycling (GR) were reversed/increased by sulforaphane treatment. Antiferroptotic effect of sulforaphane in the diabetic liver was further evidenced through the increased level of glutathione, decreased accumulation of liable iron and lipid peroxides (4-HNE) and decreased tissue damage (fibrosis and infiltration). Finally, diabetes-induced increase in serum glucose, ALT, AST and triglyceride level was significantly reduced by   sulforaphane.
These findings revealed for the first time that sulforaphane prevents in vivo diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. This suggests sulforaphane as a promising therapeutic tool for preventing ferroptosis at least in diabetes and diabetes-related pathologies.
PB  - EMBO
C3  - EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
T1  - Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis
SP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6067
ER  - 

@conference{
author = "Otašević, Vesna and Grigorov, Ilijana and Savić, Nevena and Markelić, Milica and Veličković, Ksenija and Gudelj, Anđelija and Martinović, Vesna and Stančić, Ana",
year = "2023",
abstract = "Recently, we characterized the ferroptotic phenotype of the liver of diabetic mice and revealed the inactivation of Nrf2 as an integral part of diabetes-induced liver ferroptosis. We aim here to examine does sulforaphane, an Nrf2 activator and antioxidant, prevent diabetes-induced liver ferroptosis and the mechanisms  involved.
For that purpose, male C57BL/6 mice were divided into three groups: control, diabetic (streptozotocin-treated, 40 mg/kg/5 consecutive days), diabetic+sulforaphane treated (2.5 mg/kg, from day 1-42).
Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic parameters crucial for antioxidative defense (HO-1, catalase, SOD), iron metabolism (ferroportin, ferritin), glutathione synthesis (xCT, GCLC, CTH, CBS) and recycling (GR) were reversed/increased by sulforaphane treatment. Antiferroptotic effect of sulforaphane in the diabetic liver was further evidenced through the increased level of glutathione, decreased accumulation of liable iron and lipid peroxides (4-HNE) and decreased tissue damage (fibrosis and infiltration). Finally, diabetes-induced increase in serum glucose, ALT, AST and triglyceride level was significantly reduced by   sulforaphane.
These findings revealed for the first time that sulforaphane prevents in vivo diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. This suggests sulforaphane as a promising therapeutic tool for preventing ferroptosis at least in diabetes and diabetes-related pathologies.",
publisher = "EMBO",
journal = "EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany",
title = "Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis",
pages = "91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6067"
}

Otašević, V., Grigorov, I., Savić, N., Markelić, M., Veličković, K., Gudelj, A., Martinović, V.,& Stančić, A.. (2023). Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
EMBO., 91.
https://hdl.handle.net/21.15107/rcub_ibiss_6067

Otašević V, Grigorov I, Savić N, Markelić M, Veličković K, Gudelj A, Martinović V, Stančić A. Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany. 2023;:91.
https://hdl.handle.net/21.15107/rcub_ibiss_6067 .

Otašević, Vesna, Grigorov, Ilijana, Savić, Nevena, Markelić, Milica, Veličković, Ksenija, Gudelj, Anđelija, Martinović, Vesna, Stančić, Ana, "Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis" in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany (2023):91,
https://hdl.handle.net/21.15107/rcub_ibiss_6067 .

TY  - CONF
AU  - Savić, Nevena
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Stančić, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5195
AB  - Један од узрока патолошких промена јетре током Diabetes mellitus-a (ДМ) јесте повећање ћелијске смрти. До данас је описана апоптоза, некроза и аутофагија хепатоцита.1 Циљ ове студије био је испитивање укључености фероптозе, ћелијске смрти која настаје услед интезивираног процеса липидне пероксидације зависне од гвожђа, на развој патолошких промена јетре у ДМ, коришћењем фероптотског инхибитора феростатина-1 (Фер-1). Мужјаци C57BL/6 мишева подељени су у три групе: 1. контрола (К); 2. дијабетeс (индукован стрептозотоцином, Д) и 3. дијабетес + Фер-1 (ДФ). У групи Д забележена је смањена експресија цитопротективног транскрипционог фактора Nrf2 (енгл. nuclear factor (erythroid-derived-2)-related factor2), што је случај и са његовим таргетним протеинима битним за регулисање процеса фероптозе, као што су кључни ензим за уклањање липидних пероксида, GPx4 (глутатион пероксидаза 4), цистеин-глутаматни трансмембрански антипортер (xCT) укључен у регулацију метаболизма глутатиона и хем оксигеназа 1 (HO-1) која регулише метаболизам гвожђа. У групи ДФ забележено је значајно повећање експресије Nrf2, GPx4, xCT и HO-1. Маркер липидне пероксидације 4-HNE повећан је у хепатоцитима Д групе, а смањен у ДФ групи. Наши резултати показују да хепатоцити у ДМ подлежу фероптози, с обзиром на чињеницу да Фер-1 делује цитопротективно, активирајући Nrf2-зависну сигналну каскаду. Ово нас упућује на фероптозу као нову терапеутску мету у лечењу патолошких промена јетре у ДМ и то стимулисаном активацијом Nrf2.
AB  - Jedan od uzroka patoloških promena jetre tokom Diabetes mellitus-a (DM) jeste povećanje ćelijske smrti. Do danas je opisana apoptoza, nekroza i autofagija hepatocita.1 Cilj ove studije bio je ispitivanje uključenosti feroptoze, ćelijske smrti koja nastaje usled inteziviranog procesa lipidne peroksidacije zavisne od gvožđa, na razvoj patoloških promena jetre u DM, korišćenjem feroptotskog inhibitora ferostatina-1 (Fer-1). Mužjaci C57BL/6 miševa podeljeni su u tri grupe: 1. kontrola (K); 2. dijabetes (indukovan streptozotocinom, D) i 3. dijabetes + Fer-1 (DF). U grupi D zabeležena je smanjena ekspresija citoprotektivnog transkripcionog faktora Nrf2 (engl. nuclear factor (erythroid-derived-2)-related factor2), što je slučaj i sa njegovim targetnim proteinima bitnim za regulisanje procesa feroptoze, kao što su ključni enzim za uklanjanje lipidnih peroksida, GPx4 (glutation peroksidaza 4), cistein-glutamatni transmembranski antiporter (xCT) uključen u regulaciju metabolizma glutationa i hem oksigenaza 1 (HO-1) koja reguliše metabolizam gvožđa. U grupi DF zabeleženo je značajno povećanje ekspresije Nrf2, GPx4, xCT i HO-1. Marker lipidne peroksidacije 4-HNE povećan je u hepatocitima D grupe, a smanjen u DF grupi. Naši rezultati pokazuju da hepatociti u DM podležu feroptozi, s obzirom na činjenicu da Fer-1 deluje citoprotektivno, aktivirajući Nrf2-zavisnu signalnu kaskadu. Ovo nas upućuje na feroptozu kao novu terapeutsku metu u lečenju patoloških promena jetre u DM i to stimulisanom aktivacijom Nrf2.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Допринос фероптозе патолошким променама јетре дијабетичних мишева
T1  - Doprinos feroptoze patološkim promenama jetre dijabetičnih miševa
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5195
ER  - 

@conference{
author = "Savić, Nevena and Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Grigorov, Ilijana and Veličković, Ksenija and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Stančić, Ana",
year = "2022",
abstract = "Један од узрока патолошких промена јетре током Diabetes mellitus-a (ДМ) јесте повећање ћелијске смрти. До данас је описана апоптоза, некроза и аутофагија хепатоцита.1 Циљ ове студије био је испитивање укључености фероптозе, ћелијске смрти која настаје услед интезивираног процеса липидне пероксидације зависне од гвожђа, на развој патолошких промена јетре у ДМ, коришћењем фероптотског инхибитора феростатина-1 (Фер-1). Мужјаци C57BL/6 мишева подељени су у три групе: 1. контрола (К); 2. дијабетeс (индукован стрептозотоцином, Д) и 3. дијабетес + Фер-1 (ДФ). У групи Д забележена је смањена експресија цитопротективног транскрипционог фактора Nrf2 (енгл. nuclear factor (erythroid-derived-2)-related factor2), што је случај и са његовим таргетним протеинима битним за регулисање процеса фероптозе, као што су кључни ензим за уклањање липидних пероксида, GPx4 (глутатион пероксидаза 4), цистеин-глутаматни трансмембрански антипортер (xCT) укључен у регулацију метаболизма глутатиона и хем оксигеназа 1 (HO-1) која регулише метаболизам гвожђа. У групи ДФ забележено је значајно повећање експресије Nrf2, GPx4, xCT и HO-1. Маркер липидне пероксидације 4-HNE повећан је у хепатоцитима Д групе, а смањен у ДФ групи. Наши резултати показују да хепатоцити у ДМ подлежу фероптози, с обзиром на чињеницу да Фер-1 делује цитопротективно, активирајући Nrf2-зависну сигналну каскаду. Ово нас упућује на фероптозу као нову терапеутску мету у лечењу патолошких промена јетре у ДМ и то стимулисаном активацијом Nrf2., Jedan od uzroka patoloških promena jetre tokom Diabetes mellitus-a (DM) jeste povećanje ćelijske smrti. Do danas je opisana apoptoza, nekroza i autofagija hepatocita.1 Cilj ove studije bio je ispitivanje uključenosti feroptoze, ćelijske smrti koja nastaje usled inteziviranog procesa lipidne peroksidacije zavisne od gvožđa, na razvoj patoloških promena jetre u DM, korišćenjem feroptotskog inhibitora ferostatina-1 (Fer-1). Mužjaci C57BL/6 miševa podeljeni su u tri grupe: 1. kontrola (K); 2. dijabetes (indukovan streptozotocinom, D) i 3. dijabetes + Fer-1 (DF). U grupi D zabeležena je smanjena ekspresija citoprotektivnog transkripcionog faktora Nrf2 (engl. nuclear factor (erythroid-derived-2)-related factor2), što je slučaj i sa njegovim targetnim proteinima bitnim za regulisanje procesa feroptoze, kao što su ključni enzim za uklanjanje lipidnih peroksida, GPx4 (glutation peroksidaza 4), cistein-glutamatni transmembranski antiporter (xCT) uključen u regulaciju metabolizma glutationa i hem oksigenaza 1 (HO-1) koja reguliše metabolizam gvožđa. U grupi DF zabeleženo je značajno povećanje ekspresije Nrf2, GPx4, xCT i HO-1. Marker lipidne peroksidacije 4-HNE povećan je u hepatocitima D grupe, a smanjen u DF grupi. Naši rezultati pokazuju da hepatociti u DM podležu feroptozi, s obzirom na činjenicu da Fer-1 deluje citoprotektivno, aktivirajući Nrf2-zavisnu signalnu kaskadu. Ovo nas upućuje na feroptozu kao novu terapeutsku metu u lečenju patoloških promena jetre u DM i to stimulisanom aktivacijom Nrf2.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Допринос фероптозе патолошким променама јетре дијабетичних мишева, Doprinos feroptoze patološkim promenama jetre dijabetičnih miševa",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5195"
}

Savić, N., Otašević, V., Saksida, T., Markelić, M., Grigorov, I., Veličković, K., Martinović, V., Mićanović, D., Ivanović, A.,& Stančić, A.. (2022). Допринос фероптозе патолошким променама јетре дијабетичних мишева. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society..
https://hdl.handle.net/21.15107/rcub_ibiss_5195

Savić N, Otašević V, Saksida T, Markelić M, Grigorov I, Veličković K, Martinović V, Mićanović D, Ivanović A, Stančić A. Допринос фероптозе патолошким променама јетре дијабетичних мишева. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5195 .

Savić, Nevena, Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Grigorov, Ilijana, Veličković, Ksenija, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Stančić, Ana, "Допринос фероптозе патолошким променама јетре дијабетичних мишева" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5195 .

TY  - CONF
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Vučetić, Milica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Savić, Nevena
AU  - Stančić, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5197
AB  - Кључни патолошки догађај у настанку дијабетеса је губитак функционалних β-ћелија. Улога фероптозе, новоописаног типа регулисане ћелијске смрти зависне од гвожђа, у смањењу популације β-ћелија код дијабетеса није довољно испитана. Стога је у овом раду испитиван допринос фероптозе умирању β-ћелија у дијабетичним условима in vivo и in vitro. Код мишева са дијабетесом индукованим стрептозотоцином, СТЗ забележено је значајно повећање инфилтрације макрофага и акумулације липидних пероксида у острвцима панкреаса, праћено смањењем популације инсулин позитивних ћелија, експресије глутатион пероксидазе 4, GPX4, цистеин/глутамат транспортера xCT и хем оксигеназе 1. Резултати добијени in vitro на Rin-5f β-ћелијама су показали да дијабетични услови (висока концентрација глукозе, СТЗ, цитокини и водоник пероксид снижавају експресију транскрипционог фактора Nrf2, GPX4 и митохондријални мембрански потенцијал, а повећавају продукцију реактивних врста кисеоника, акумулацију слободног гвожђа, липидних пероксида и смртност β-ћелија. Примена инхибитора фероптозе, феростатина-1 у потпуности је поништила наведене промене, тј. остварила позитивне ефекте на β-ћелије/панкреас дијабетичних животиња, осим у случају in vitro третмана цитокинима, указујући на разлике између дијабетогених стимулуса у одређивању судбине β-ћелија. Наведени резултати показују да модулирање тј. инхибиција фероптозе у дијабетесу може бити нови обећавајући приступ за очување популације β-ћелија и третман дијабетеса.
AB  - Ključni patološki događaj u nastanku dijabetesa je gubitak funkcionalnih β-ćelija. Uloga feroptoze, novoopisanog tipa regulisane ćelijske smrti zavisne od gvožđa, u smanjenju populacije β-ćelija kod dijabetesa nije dovoljno ispitana. Stoga je u ovom radu ispitivan doprinos feroptoze umiranju β-ćelija u dijabetičnim uslovima in vivo i in vitro. Kod miševa sa dijabetesom indukovanim streptozotocinom, STZ zabeleženo je značajno povećanje infiltracije makrofaga i akumulacije lipidnih peroksida u ostrvcima pankreasa, praćeno smanjenjem populacije insulin pozitivnih ćelija, ekspresije glutation peroksidaze 4, GPX4, cistein/glutamat transportera xCT i hem oksigenaze 1. Rezultati dobijeni in vitro na Rin-5f β-ćelijama su pokazali da dijabetični uslovi (visoka koncentracija glukoze, STZ, citokini i vodonik peroksid snižavaju ekspresiju transkripcionog faktora Nrf2, GPX4 i mitohondrijalni membranski potencijal, a povećavaju produkciju reaktivnih vrsta kiseonika, akumulaciju slobodnog gvožđa, lipidnih peroksida i smrtnost β-ćelija. Primena inhibitora feroptoze, ferostatina-1 u potpunosti je poništila navedene promene, tj. ostvarila pozitivne efekte na β-ćelije/pankreas dijabetičnih životinja, osim u slučaju in vitro tretmana citokinima, ukazujući na razlike između dijabetogenih stimulusa u određivanju sudbine β-ćelija. Navedeni rezultati pokazuju da moduliranje tj. inhibicija feroptoze u dijabetesu može biti novi obećavajući pristup za očuvanje populacije β-ćelija i tretman dijabetesa.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Фероптоза у дијабетесу и дијабетичним компликацијама
T1  - Feroptoza u dijabetesu i dijabetičnim komplikacijama
SP  - 279
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5197
ER  - 

@conference{
author = "Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Grigorov, Ilijana and Vučetić, Milica and Veličković, Ksenija and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Savić, Nevena and Stančić, Ana",
year = "2022",
abstract = "Кључни патолошки догађај у настанку дијабетеса је губитак функционалних β-ћелија. Улога фероптозе, новоописаног типа регулисане ћелијске смрти зависне од гвожђа, у смањењу популације β-ћелија код дијабетеса није довољно испитана. Стога је у овом раду испитиван допринос фероптозе умирању β-ћелија у дијабетичним условима in vivo и in vitro. Код мишева са дијабетесом индукованим стрептозотоцином, СТЗ забележено је значајно повећање инфилтрације макрофага и акумулације липидних пероксида у острвцима панкреаса, праћено смањењем популације инсулин позитивних ћелија, експресије глутатион пероксидазе 4, GPX4, цистеин/глутамат транспортера xCT и хем оксигеназе 1. Резултати добијени in vitro на Rin-5f β-ћелијама су показали да дијабетични услови (висока концентрација глукозе, СТЗ, цитокини и водоник пероксид снижавају експресију транскрипционог фактора Nrf2, GPX4 и митохондријални мембрански потенцијал, а повећавају продукцију реактивних врста кисеоника, акумулацију слободног гвожђа, липидних пероксида и смртност β-ћелија. Примена инхибитора фероптозе, феростатина-1 у потпуности је поништила наведене промене, тј. остварила позитивне ефекте на β-ћелије/панкреас дијабетичних животиња, осим у случају in vitro третмана цитокинима, указујући на разлике између дијабетогених стимулуса у одређивању судбине β-ћелија. Наведени резултати показују да модулирање тј. инхибиција фероптозе у дијабетесу може бити нови обећавајући приступ за очување популације β-ћелија и третман дијабетеса., Ključni patološki događaj u nastanku dijabetesa je gubitak funkcionalnih β-ćelija. Uloga feroptoze, novoopisanog tipa regulisane ćelijske smrti zavisne od gvožđa, u smanjenju populacije β-ćelija kod dijabetesa nije dovoljno ispitana. Stoga je u ovom radu ispitivan doprinos feroptoze umiranju β-ćelija u dijabetičnim uslovima in vivo i in vitro. Kod miševa sa dijabetesom indukovanim streptozotocinom, STZ zabeleženo je značajno povećanje infiltracije makrofaga i akumulacije lipidnih peroksida u ostrvcima pankreasa, praćeno smanjenjem populacije insulin pozitivnih ćelija, ekspresije glutation peroksidaze 4, GPX4, cistein/glutamat transportera xCT i hem oksigenaze 1. Rezultati dobijeni in vitro na Rin-5f β-ćelijama su pokazali da dijabetični uslovi (visoka koncentracija glukoze, STZ, citokini i vodonik peroksid snižavaju ekspresiju transkripcionog faktora Nrf2, GPX4 i mitohondrijalni membranski potencijal, a povećavaju produkciju reaktivnih vrsta kiseonika, akumulaciju slobodnog gvožđa, lipidnih peroksida i smrtnost β-ćelija. Primena inhibitora feroptoze, ferostatina-1 u potpunosti je poništila navedene promene, tj. ostvarila pozitivne efekte na β-ćelije/pankreas dijabetičnih životinja, osim u slučaju in vitro tretmana citokinima, ukazujući na razlike između dijabetogenih stimulusa u određivanju sudbine β-ćelija. Navedeni rezultati pokazuju da moduliranje tj. inhibicija feroptoze u dijabetesu može biti novi obećavajući pristup za očuvanje populacije β-ćelija i tretman dijabetesa.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Фероптоза у дијабетесу и дијабетичним компликацијама, Feroptoza u dijabetesu i dijabetičnim komplikacijama",
pages = "279",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5197"
}

Otašević, V., Saksida, T., Markelić, M., Grigorov, I., Vučetić, M., Veličković, K., Martinović, V., Mićanović, D., Ivanović, A., Savić, N.,& Stančić, A.. (2022). Фероптоза у дијабетесу и дијабетичним компликацијама. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 279.
https://hdl.handle.net/21.15107/rcub_ibiss_5197

Otašević V, Saksida T, Markelić M, Grigorov I, Vučetić M, Veličković K, Martinović V, Mićanović D, Ivanović A, Savić N, Stančić A. Фероптоза у дијабетесу и дијабетичним компликацијама. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:279.
https://hdl.handle.net/21.15107/rcub_ibiss_5197 .

Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Grigorov, Ilijana, Vučetić, Milica, Veličković, Ksenija, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Savić, Nevena, Stančić, Ana, "Фероптоза у дијабетесу и дијабетичним компликацијама" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):279,
https://hdl.handle.net/21.15107/rcub_ibiss_5197 .

TY  - JOUR
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Saksida, Tamara
AU  - Savić, Nevena
AU  - Vučetić, Milica
AU  - Martinović, Vesna
AU  - Ivanović, Anđelija
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5160
AB  - Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause  -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves  -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Involvement of Ferroptosis in Diabetes-Induced Liver Pathology
IS  - 16
VL  - 23
DO  - 10.3390/ijms23169309
SP  - 9309
ER  - 

@article{
author = "Stančić, Ana and Veličković, Ksenija and Markelić, Milica and Grigorov, Ilijana and Saksida, Tamara and Savić, Nevena and Vučetić, Milica and Martinović, Vesna and Ivanović, Anđelija and Otašević, Vesna",
year = "2022",
abstract = "Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause  -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves  -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology",
number = "16",
volume = "23",
doi = "10.3390/ijms23169309",
pages = "9309"
}

Stančić, A., Veličković, K., Markelić, M., Grigorov, I., Saksida, T., Savić, N., Vučetić, M., Martinović, V., Ivanović, A.,& Otašević, V.. (2022). Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 9309.
https://doi.org/10.3390/ijms23169309

Stančić A, Veličković K, Markelić M, Grigorov I, Saksida T, Savić N, Vučetić M, Martinović V, Ivanović A, Otašević V. Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. in International Journal of Molecular Sciences. 2022;23(16):9309.
doi:10.3390/ijms23169309 .

Stančić, Ana, Veličković, Ksenija, Markelić, Milica, Grigorov, Ilijana, Saksida, Tamara, Savić, Nevena, Vučetić, Milica, Martinović, Vesna, Ivanović, Anđelija, Otašević, Vesna, "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology" in International Journal of Molecular Sciences, 23, no. 16 (2022):9309,
https://doi.org/10.3390/ijms23169309 . .

TY  - CONF
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Otašević, Vesna
PY  - 2022
UR  - https://meetings.embo.org/event/22-thiol-oxidation
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5264
AB  - Diabetes is considered as an important cause of wide spectrum of liver disorders with the significant implication of oxidative stress. Cell death assumes a central role in the etiology of most of the liver pathologies. We aim to describe here the ferroptotic phenotype in diabetic liver. For that purpose, male C57BL/6 mice were divided into three groups: diabetic (streptozotocin-treated, 40 mg/kg in 5 consecutive days), diabetic treated with ferrostatin-1 (Fer-1, 1 mg/kg, from day 1-21) and vehicle-treated (control) animals. Diabetes induced biochemical/morphological alterations in the liver, including increases in ALT and TGC levels as well as fibrosis, hepatocytes volume and number of binuclear cells. These were accompanied by following changes at the molecular level: i) increase in accumulation of prooxidative (such as iron, lipofuscin and 4-HNE) and proinflammatory (HMGB1) parameters and ii) decrease in antioxidative-related (Nrf2, xCT, GPX4, GCL, HO-1) parameters. All of these ferroptosis-related events in the liver of diabetic animals were diminished with Fer-1 treatment. Our study reveals ferroptotic phenotype as an important part of the diabetes-related pathological changes in the liver. Also, the results suggest that targeting of ferroptosis represents promising approach in the prevention and treatment of liver diseases accompanying diabetes.
PB  - Heidelberg: European Molecular Biology Organization (EMBO)
C3  - EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain
T1  - Characterization of ferroptosis in diabetic liver
SP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5264
ER  - 

@conference{
author = "Stančić, Ana and Veličković, Ksenija and Markelić, Milica and Grigorov, Ilijana and Martinović, Vesna and Otašević, Vesna",
year = "2022",
abstract = "Diabetes is considered as an important cause of wide spectrum of liver disorders with the significant implication of oxidative stress. Cell death assumes a central role in the etiology of most of the liver pathologies. We aim to describe here the ferroptotic phenotype in diabetic liver. For that purpose, male C57BL/6 mice were divided into three groups: diabetic (streptozotocin-treated, 40 mg/kg in 5 consecutive days), diabetic treated with ferrostatin-1 (Fer-1, 1 mg/kg, from day 1-21) and vehicle-treated (control) animals. Diabetes induced biochemical/morphological alterations in the liver, including increases in ALT and TGC levels as well as fibrosis, hepatocytes volume and number of binuclear cells. These were accompanied by following changes at the molecular level: i) increase in accumulation of prooxidative (such as iron, lipofuscin and 4-HNE) and proinflammatory (HMGB1) parameters and ii) decrease in antioxidative-related (Nrf2, xCT, GPX4, GCL, HO-1) parameters. All of these ferroptosis-related events in the liver of diabetic animals were diminished with Fer-1 treatment. Our study reveals ferroptotic phenotype as an important part of the diabetes-related pathological changes in the liver. Also, the results suggest that targeting of ferroptosis represents promising approach in the prevention and treatment of liver diseases accompanying diabetes.",
publisher = "Heidelberg: European Molecular Biology Organization (EMBO)",
journal = "EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain",
title = "Characterization of ferroptosis in diabetic liver",
pages = "51",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5264"
}

Stančić, A., Veličković, K., Markelić, M., Grigorov, I., Martinović, V.,& Otašević, V.. (2022). Characterization of ferroptosis in diabetic liver. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain
Heidelberg: European Molecular Biology Organization (EMBO)., 51.
https://hdl.handle.net/21.15107/rcub_ibiss_5264

Stančić A, Veličković K, Markelić M, Grigorov I, Martinović V, Otašević V. Characterization of ferroptosis in diabetic liver. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain. 2022;:51.
https://hdl.handle.net/21.15107/rcub_ibiss_5264 .

Stančić, Ana, Veličković, Ksenija, Markelić, Milica, Grigorov, Ilijana, Martinović, Vesna, Otašević, Vesna, "Characterization of ferroptosis in diabetic liver" in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain (2022):51,
https://hdl.handle.net/21.15107/rcub_ibiss_5264 .

TY  - CONF
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Otašević, Vesna
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4899
AB  - Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Ferroptosis as a novel determinant of β-cell death in diabetic conditions
SP  - 146
EP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4899
ER  - 

@conference{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Ivanović, Anđelija and Veličković, Ksenija and Otašević, Vesna",
year = "2021",
abstract = "Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Ferroptosis as a novel determinant of β-cell death in diabetic conditions",
pages = "146-147",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4899"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Ivanović, A., Veličković, K.,& Otašević, V.. (2021). Ferroptosis as a novel determinant of β-cell death in diabetic conditions. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 146-147.
https://hdl.handle.net/21.15107/rcub_ibiss_4899

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Ivanović A, Veličković K, Otašević V. Ferroptosis as a novel determinant of β-cell death in diabetic conditions. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:146-147.
https://hdl.handle.net/21.15107/rcub_ibiss_4899 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Ivanović, Anđelija, Veličković, Ksenija, Otašević, Vesna, "Ferroptosis as a novel determinant of β-cell death in diabetic conditions" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):146-147,
https://hdl.handle.net/21.15107/rcub_ibiss_4899 .

TY  - CONF
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Veličković, Ksenija
AU  - Otašević, Vesna
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4897
AB  - Feroptosis is a recently described, programmed form of cell death. It is iron-dependant and characterized by the accumulation of lipid peroxides and reactive species. The main pathological hallmark of diabetes is -cell loss, and so far, several types of -cell death have been described. However, involvement of ferroptosis in -cell loss induced by diabetogenic factors is still unexplored.
The aim of this study was to investigate potential involvement of ferroptosis in the regulation of -cell loss in diabetes.For that purpose Rin-5F pancreatic -cells were treated with well-known diabetes-mimicking agents: high glucose (HG; 25 mM), hydrogen peroxide (H2O2; 75 μM) and streptozotocin (STZ; 10 mM) ) for 12h in the absence or presence of ferrostosis inhibitor, ferrostatin-1 (Fer-1, 1.5 μM). As a positive control, an inducer of ferroptosis RSL3 (3 μM) was used. Cells were prepared for flow citometry (death cell assay propidium iodide (PI) staining; dihydrorhodamine 123 (DHR) reactive oxygen species (ROS) detection) and microscopic analyses (phase contrast analysis of cells viability, morphology and cell confluence; Sudan III detection of neutral lipids and lipofuscin; Prussian blue detection of intracellular iron accumulation; C11-BODIPY detection of lipid peroxides and immunofluorescence detection of phospho-NFE2-related factor 2 (pNrf2)).Our results demonstrated that mimicking diabetic microenvironment by HG, STZ and H2O2 induced ferroptosis of -cells in vitro (Fig. 1), since observed alterations were similar to those induced by RSL3. As we observed microscopically, total cell number decreased, percentage of dead PI+ cells increased and cell changed their morphology from typical to spherical and detached. In addition, increased accumulation of lipid peroxides, ROS, lipids and/or lipofuscin and iron were observed after these treatments. Fer-1 rescued cells from death after all treatments, along with abolishing the effects of those treatments on ROS, lipid peroxides and iron content. Further, Fer-1-induced activation of Nrf2, which is well known as an antioxidant transcriptional factor that regulates level of many of the ferroptosis-related molecules including those involved in metabolism of GSH, iron and lipids. Taken together, our results demonstrated ferroptosis involvement in the -cell loss under diabetogenic conditions, thus proposing it as a new potential target in the diabetes therapy approach.
C3  - MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online
T1  - Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro
SP  - 641
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4897
ER  - 

@conference{
author = "Markelić, Milica and Stančić, Ana and Saksida, Tamara and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Veličković, Ksenija and Otašević, Vesna",
year = "2021",
abstract = "Feroptosis is a recently described, programmed form of cell death. It is iron-dependant and characterized by the accumulation of lipid peroxides and reactive species. The main pathological hallmark of diabetes is -cell loss, and so far, several types of -cell death have been described. However, involvement of ferroptosis in -cell loss induced by diabetogenic factors is still unexplored.
The aim of this study was to investigate potential involvement of ferroptosis in the regulation of -cell loss in diabetes.For that purpose Rin-5F pancreatic -cells were treated with well-known diabetes-mimicking agents: high glucose (HG; 25 mM), hydrogen peroxide (H2O2; 75 μM) and streptozotocin (STZ; 10 mM) ) for 12h in the absence or presence of ferrostosis inhibitor, ferrostatin-1 (Fer-1, 1.5 μM). As a positive control, an inducer of ferroptosis RSL3 (3 μM) was used. Cells were prepared for flow citometry (death cell assay propidium iodide (PI) staining; dihydrorhodamine 123 (DHR) reactive oxygen species (ROS) detection) and microscopic analyses (phase contrast analysis of cells viability, morphology and cell confluence; Sudan III detection of neutral lipids and lipofuscin; Prussian blue detection of intracellular iron accumulation; C11-BODIPY detection of lipid peroxides and immunofluorescence detection of phospho-NFE2-related factor 2 (pNrf2)).Our results demonstrated that mimicking diabetic microenvironment by HG, STZ and H2O2 induced ferroptosis of -cells in vitro (Fig. 1), since observed alterations were similar to those induced by RSL3. As we observed microscopically, total cell number decreased, percentage of dead PI+ cells increased and cell changed their morphology from typical to spherical and detached. In addition, increased accumulation of lipid peroxides, ROS, lipids and/or lipofuscin and iron were observed after these treatments. Fer-1 rescued cells from death after all treatments, along with abolishing the effects of those treatments on ROS, lipid peroxides and iron content. Further, Fer-1-induced activation of Nrf2, which is well known as an antioxidant transcriptional factor that regulates level of many of the ferroptosis-related molecules including those involved in metabolism of GSH, iron and lipids. Taken together, our results demonstrated ferroptosis involvement in the -cell loss under diabetogenic conditions, thus proposing it as a new potential target in the diabetes therapy approach.",
journal = "MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online",
title = "Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro",
pages = "641",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4897"
}

Markelić, M., Stančić, A., Saksida, T., Vučetić, M., Grigorov, I., Martinović, V., Veličković, K.,& Otašević, V.. (2021). Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro. in MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online, 641.
https://hdl.handle.net/21.15107/rcub_ibiss_4897

Markelić M, Stančić A, Saksida T, Vučetić M, Grigorov I, Martinović V, Veličković K, Otašević V. Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro. in MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online. 2021;:641.
https://hdl.handle.net/21.15107/rcub_ibiss_4897 .

Markelić, Milica, Stančić, Ana, Saksida, Tamara, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Veličković, Ksenija, Otašević, Vesna, "Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro" in MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online (2021):641,
https://hdl.handle.net/21.15107/rcub_ibiss_4897 .

TY  - JOUR
AU  - Otašević, Vesna
AU  - Šurlan, Lela
AU  - Vučetić, Milica
AU  - Tulić, Ivan
AU  - Buzadžić, Biljana
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Veličković, Ksenija
AU  - Golić, Igor
AU  - Markelić, Milica
AU  - Korać, Aleksandra
AU  - Korać, Bato
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6213
AB  - Developmental dysfunction in embryos, such as a lethal level of fragmentation, is assumed to be mitochondrial in origin. This study investigated the molecular basis of mitochondrial impairment in embryo fragmentation. Transcription patterns of factors that determine mitochondrial functionality: (i) components of the oxidative phosphorylation (OXPHOS) - complex I, cytochrome b, complex IV and ATP synthase; (ii) mitochondrial membrane potential (MMP); (iii) mitochondrial DNA (mtDNA) content and (iv) proteins involved in mitochondrial dynamics, mitofusin 1 (Mfn1) and dynamin related protein 1 (Drp1) were examined in six-cells Day 3 non-fragmented (control), low-fragmented (LF) and high-fragmented (HF) human embryos. Gene expression of mitochondria-encoded components of complex I and IV, cytochrome b and mtDNA were increased in HF embryos compared with control and LF embryos. In LF embryos, expression of these molecules was decreased compared with control and HF embryos. Both classes of fragmented embryos had decreased MMP compared with control. LF embryos had increased gene expression of Mfn1 accompanied by decreased expression of Drp1, while HF embryos had decreased Mfn1 expression but increased Drp1 expression. The study revealed that each improper transcriptional (in)activation of mitochondria-encoded components of the OXPHOS during early in vitro embryo development is associated with a decrease in MMP and with embryo fragmentation. The results also showed the importance of mitochondrial dynamics in fragmentation, at least in the extent of this process.
PB  - CSIRO Publishing
T2  - Reproduction, Fertility and Development
T1  - Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation
IS  - 3
VL  - 28
DO  - 10.1071/RD13415
SP  - 319
EP  - 327
ER  - 

@article{
author = "Otašević, Vesna and Šurlan, Lela and Vučetić, Milica and Tulić, Ivan and Buzadžić, Biljana and Stančić, Ana and Janković, Aleksandra and Veličković, Ksenija and Golić, Igor and Markelić, Milica and Korać, Aleksandra and Korać, Bato",
year = "2016",
abstract = "Developmental dysfunction in embryos, such as a lethal level of fragmentation, is assumed to be mitochondrial in origin. This study investigated the molecular basis of mitochondrial impairment in embryo fragmentation. Transcription patterns of factors that determine mitochondrial functionality: (i) components of the oxidative phosphorylation (OXPHOS) - complex I, cytochrome b, complex IV and ATP synthase; (ii) mitochondrial membrane potential (MMP); (iii) mitochondrial DNA (mtDNA) content and (iv) proteins involved in mitochondrial dynamics, mitofusin 1 (Mfn1) and dynamin related protein 1 (Drp1) were examined in six-cells Day 3 non-fragmented (control), low-fragmented (LF) and high-fragmented (HF) human embryos. Gene expression of mitochondria-encoded components of complex I and IV, cytochrome b and mtDNA were increased in HF embryos compared with control and LF embryos. In LF embryos, expression of these molecules was decreased compared with control and HF embryos. Both classes of fragmented embryos had decreased MMP compared with control. LF embryos had increased gene expression of Mfn1 accompanied by decreased expression of Drp1, while HF embryos had decreased Mfn1 expression but increased Drp1 expression. The study revealed that each improper transcriptional (in)activation of mitochondria-encoded components of the OXPHOS during early in vitro embryo development is associated with a decrease in MMP and with embryo fragmentation. The results also showed the importance of mitochondrial dynamics in fragmentation, at least in the extent of this process.",
publisher = "CSIRO Publishing",
journal = "Reproduction, Fertility and Development",
title = "Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation",
number = "3",
volume = "28",
doi = "10.1071/RD13415",
pages = "319-327"
}

Otašević, V., Šurlan, L., Vučetić, M., Tulić, I., Buzadžić, B., Stančić, A., Janković, A., Veličković, K., Golić, I., Markelić, M., Korać, A.,& Korać, B.. (2016). Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation. in Reproduction, Fertility and Development
CSIRO Publishing., 28(3), 319-327.
https://doi.org/10.1071/RD13415

Otašević V, Šurlan L, Vučetić M, Tulić I, Buzadžić B, Stančić A, Janković A, Veličković K, Golić I, Markelić M, Korać A, Korać B. Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation. in Reproduction, Fertility and Development. 2016;28(3):319-327.
doi:10.1071/RD13415 .

Otašević, Vesna, Šurlan, Lela, Vučetić, Milica, Tulić, Ivan, Buzadžić, Biljana, Stančić, Ana, Janković, Aleksandra, Veličković, Ksenija, Golić, Igor, Markelić, Milica, Korać, Aleksandra, Korać, Bato, "Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation" in Reproduction, Fertility and Development, 28, no. 3 (2016):319-327,
https://doi.org/10.1071/RD13415 . .

TY  - JOUR
AU  - Veličković, Ksenija
AU  - Čvoro, Aleksandra
AU  - Srdić, Biljana
AU  - Stokić, Edita
AU  - Markelić, Milica
AU  - Golić, Igor
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
AU  - Korać, Aleksandra
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2294
AB  - Context: Brown adipose tissue (BAT) has the unique ability of generating
   heat due to the expression of mitochondrial uncoupling protein 1 (UCP1).
   A recent discovery regarding functional BAT in adult humans has
   increased interest in the molecular pathways of BAT development and
   functionality. An important role for estrogen in white adipose tissue
   was shown, but the possible role of estrogen in human fetal BAT (fBAT)
   is unclear.
   Objective: The objective of this study was to determine whether human
   fBAT expresses estrogen receptor alpha (ER alpha) and ER beta. In
   addition, we examined their localization as well as their correlation
   with crucial proteins involved in BAT differentiation, proliferation,
   mitochondriogenesis and thermogenesis including peroxisome
   proliferator-activated receptor gamma (PPAR gamma), proliferating cell
   nuclear antigen (PCNA), PPAR gamma-coactivator-1 alpha (PGC-1 alpha),
   and UCP1.
   Design: The fBAT was obtained from 4 human male fetuses aged 15, 17, 20,
   and 23 weeks gestation. ER alpha and ER beta expression was assessed
   using Western blotting, immunohistochemistry, and immunocytochemistry.
   Possible correlations with PPAR gamma, PCNA, PGC-1 alpha, and UCP1 were
   examined by double immunofluorescence.
   Results: Both ER alpha and ER beta were expressed in human fBAT, with ER
   alpha being dominant. Unlike ER beta, which was present only in mature
   brown adipocytes, we detected ER alpha in mature adipocytes,
   preadipocytes, mesenchymal and endothelial cells. In addition, double
   immunofluorescence supported the notion that differentiation in fBAT
   probably involves ER alpha. Immunocytochemical analysis revealed
   mitochondrial localization of both receptors.
   Conclusion: The expression of both ER alpha and ER beta in human fBAT
   suggests a role for estrogen in its development, primarily via ER alpha.
   In addition, our results indicate that fBAT mitochondria could be
   targeted by estrogens and pointed out the possible role of both ERs in
   mitochondriogenesis.
T2  - Journal of Clinical Endocrinology & Metabolism
T1  - Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue
IS  - 1
VL  - 99
DO  - 10.1210/jc.2013-2017
SP  - 151
EP  - 159
ER  - 

@article{
author = "Veličković, Ksenija and Čvoro, Aleksandra and Srdić, Biljana and Stokić, Edita and Markelić, Milica and Golić, Igor and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Vučetić, Milica and Buzadžić, Biljana J. and Korać, Bato and Korać, Aleksandra",
year = "2014",
abstract = "Context: Brown adipose tissue (BAT) has the unique ability of generating
   heat due to the expression of mitochondrial uncoupling protein 1 (UCP1).
   A recent discovery regarding functional BAT in adult humans has
   increased interest in the molecular pathways of BAT development and
   functionality. An important role for estrogen in white adipose tissue
   was shown, but the possible role of estrogen in human fetal BAT (fBAT)
   is unclear.
   Objective: The objective of this study was to determine whether human
   fBAT expresses estrogen receptor alpha (ER alpha) and ER beta. In
   addition, we examined their localization as well as their correlation
   with crucial proteins involved in BAT differentiation, proliferation,
   mitochondriogenesis and thermogenesis including peroxisome
   proliferator-activated receptor gamma (PPAR gamma), proliferating cell
   nuclear antigen (PCNA), PPAR gamma-coactivator-1 alpha (PGC-1 alpha),
   and UCP1.
   Design: The fBAT was obtained from 4 human male fetuses aged 15, 17, 20,
   and 23 weeks gestation. ER alpha and ER beta expression was assessed
   using Western blotting, immunohistochemistry, and immunocytochemistry.
   Possible correlations with PPAR gamma, PCNA, PGC-1 alpha, and UCP1 were
   examined by double immunofluorescence.
   Results: Both ER alpha and ER beta were expressed in human fBAT, with ER
   alpha being dominant. Unlike ER beta, which was present only in mature
   brown adipocytes, we detected ER alpha in mature adipocytes,
   preadipocytes, mesenchymal and endothelial cells. In addition, double
   immunofluorescence supported the notion that differentiation in fBAT
   probably involves ER alpha. Immunocytochemical analysis revealed
   mitochondrial localization of both receptors.
   Conclusion: The expression of both ER alpha and ER beta in human fBAT
   suggests a role for estrogen in its development, primarily via ER alpha.
   In addition, our results indicate that fBAT mitochondria could be
   targeted by estrogens and pointed out the possible role of both ERs in
   mitochondriogenesis.",
journal = "Journal of Clinical Endocrinology & Metabolism",
title = "Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue",
number = "1",
volume = "99",
doi = "10.1210/jc.2013-2017",
pages = "151-159"
}

Veličković, K., Čvoro, A., Srdić, B., Stokić, E., Markelić, M., Golić, I., Otašević, V., Stančić, A., Janković, A., Vučetić, M., Buzadžić, B. J., Korać, B.,& Korać, A.. (2014). Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue. in Journal of Clinical Endocrinology & Metabolism, 99(1), 151-159.
https://doi.org/10.1210/jc.2013-2017

Veličković K, Čvoro A, Srdić B, Stokić E, Markelić M, Golić I, Otašević V, Stančić A, Janković A, Vučetić M, Buzadžić BJ, Korać B, Korać A. Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue. in Journal of Clinical Endocrinology & Metabolism. 2014;99(1):151-159.
doi:10.1210/jc.2013-2017 .

Veličković, Ksenija, Čvoro, Aleksandra, Srdić, Biljana, Stokić, Edita, Markelić, Milica, Golić, Igor, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Vučetić, Milica, Buzadžić, Biljana J., Korać, Bato, Korać, Aleksandra, "Expression and Subcellular Localization of Estrogen Receptors alpha and
 beta in Human Fetal Brown Adipose Tissue" in Journal of Clinical Endocrinology & Metabolism, 99, no. 1 (2014):151-159,
https://doi.org/10.1210/jc.2013-2017 . .

TY  - CONF
AU  - Petrović-Kosanović, Dragana
AU  - Šošić-Jurjević, Branka
AU  - Veličković, Ksenija
AU  - Nestorović, Nataša
AU  - Ristić, Nataša
AU  - Ajdžanović, Vladimir
AU  - Jasnić, Nebojša
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6245
AB  - Hyperthermia induced by heat stress cause damages to various organs. Data on the effects of heat stress on thyroid gland are scarce, despite the fact that thyroid hormones (TH) play essential role in maintenance of thermogenesis and basal metabolic rate. In this study we examined effects of acute heat stress on thyroid histology and concentration of TH and thyrotropin (TSH) in sera. Adult male Wistar rats were divided in two groups (n=10): the first group were intact controls; the other group was exposed to ambient temperature of 30°C for 60 min in a hot chamber. Animals were decapitated immediately after exposure to heat stress. Thyroid glands were excised, weighed and prepared for further histo-morphometric analyses. Serum concentrations of TH were determined by RIA, while TSH was determined by ELISA. Acute exposure to ambient temperature of 38°C did not induce damages of thyroid tissue. Morphometric analysis revealed decreased volume density of thyroid follicles (p<0.05), while the volume density of blood vessels increased (p<0.05). Besides dilation of blood vessels, vascular congestion was also evident. Serum concentrations of TH were unchanged, while TSH increased (p<0.05). Acute exposure to moderate heat stress did not result in injuries of thyroid tissue. Still, increased volume density of blood vessels and accumulation of erythrocytes indicate thyroid blood flow. Increased blood flow, together with increased serum TSH probably contributed to increased mobilization of colloid and thyroid hormone stores under these conditions.
PB  - Belgrade: Serbian Plant Physiology Society
C3  - Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia
T1  - The effect of acute heat stress on rat pituitary-thyroid axis
SP  - 160
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6245
ER  - 

@conference{
author = "Petrović-Kosanović, Dragana and Šošić-Jurjević, Branka and Veličković, Ksenija and Nestorović, Nataša and Ristić, Nataša and Ajdžanović, Vladimir and Jasnić, Nebojša",
year = "2014",
abstract = "Hyperthermia induced by heat stress cause damages to various organs. Data on the effects of heat stress on thyroid gland are scarce, despite the fact that thyroid hormones (TH) play essential role in maintenance of thermogenesis and basal metabolic rate. In this study we examined effects of acute heat stress on thyroid histology and concentration of TH and thyrotropin (TSH) in sera. Adult male Wistar rats were divided in two groups (n=10): the first group were intact controls; the other group was exposed to ambient temperature of 30°C for 60 min in a hot chamber. Animals were decapitated immediately after exposure to heat stress. Thyroid glands were excised, weighed and prepared for further histo-morphometric analyses. Serum concentrations of TH were determined by RIA, while TSH was determined by ELISA. Acute exposure to ambient temperature of 38°C did not induce damages of thyroid tissue. Morphometric analysis revealed decreased volume density of thyroid follicles (p<0.05), while the volume density of blood vessels increased (p<0.05). Besides dilation of blood vessels, vascular congestion was also evident. Serum concentrations of TH were unchanged, while TSH increased (p<0.05). Acute exposure to moderate heat stress did not result in injuries of thyroid tissue. Still, increased volume density of blood vessels and accumulation of erythrocytes indicate thyroid blood flow. Increased blood flow, together with increased serum TSH probably contributed to increased mobilization of colloid and thyroid hormone stores under these conditions.",
publisher = "Belgrade: Serbian Plant Physiology Society",
journal = "Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia",
title = "The effect of acute heat stress on rat pituitary-thyroid axis",
pages = "160",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6245"
}

Petrović-Kosanović, D., Šošić-Jurjević, B., Veličković, K., Nestorović, N., Ristić, N., Ajdžanović, V.,& Jasnić, N.. (2014). The effect of acute heat stress on rat pituitary-thyroid axis. in Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia
Belgrade: Serbian Plant Physiology Society., 160.
https://hdl.handle.net/21.15107/rcub_ibiss_6245

Petrović-Kosanović D, Šošić-Jurjević B, Veličković K, Nestorović N, Ristić N, Ajdžanović V, Jasnić N. The effect of acute heat stress on rat pituitary-thyroid axis. in Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia. 2014;:160.
https://hdl.handle.net/21.15107/rcub_ibiss_6245 .

Petrović-Kosanović, Dragana, Šošić-Jurjević, Branka, Veličković, Ksenija, Nestorović, Nataša, Ristić, Nataša, Ajdžanović, Vladimir, Jasnić, Nebojša, "The effect of acute heat stress on rat pituitary-thyroid axis" in Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia (2014):160,
https://hdl.handle.net/21.15107/rcub_ibiss_6245 .

TY  - JOUR
AU  - Velickovic, Ksenija
AU  - Markelic, Milica
AU  - Golic, Igor
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vucetic, Milica
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
AU  - Korac, Aleksandra
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2227
AB  - Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are
   important intestinal neurotransmitters that coexist in the gut enteric
   nervous system and play an important role in intestinal physiology
   (e.g., absorption, motility, fluid secretion and smooth muscle
   relaxation). It is also known that cold exposure alters several aspects
   of gastrointestinal physiology and induces hyperphagia to meet increased
   metabolic demands, but there are no data regarding NO and VIP
   involvement in intestinal response during acclimation to cold. The
   objective of this study was to determine the influence of long-term
   l-arginine supplementation on the expression of the three isoforms of
   nitric oxide synthase (NOS) and VIP in small intestine of rats
   acclimated to room temperature or cold.
   Animals (six per group) acclimated to room temperature (22 +/- A 1 A
   degrees C) and cold (4 +/- A 1 A degrees C), respectively, were treated
   with 2.25 \% l-arginine, a substrate for NOSs, or with 0.01 \% N
   (omega)-nitro-l-arginine methyl ester, an inhibitor of NOSs, for 45
   days. The topographical distribution of VIP and NOSs expression in small
   intestine was studied by immunohistochemistry, and ImageJ software was
   used for semiquantitative densitometric analysis of their
   immunoexpression.
   Long-term dietary l-arginine supplementation increases VIP and NOSs
   immunoexpression at room temperature while at cold increases the
   endothelial NOS, inducible NOS and VIP but decrease neuronal NOS in rat
   small intestine.
   Our results demonstrate that long-term dietary l-arginine
   supplementation modulates NOSs and VIP immunoexpression in rat small
   intestine with respect to ambient temperature, pointing out the eNOS as
   a predominant NOS isoform with an immunoexpression pattern similar to
   VIP.
T2  - European Journal of Nutrition
T1  - Long-term dietary L-arginine supplementation increases endothelial
 nitric oxide synthase and vasoactive intestinal peptide immunoexpression
 in rat small intestine
IS  - 3
VL  - 53
DO  - 10.1007/s00394-013-0585-8
SP  - 813
EP  - 821
ER  - 

@article{
author = "Velickovic, Ksenija and Markelic, Milica and Golic, Igor and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Vucetic, Milica and Buzadžić, Biljana J. and Korać, Bato and Korac, Aleksandra",
year = "2014",
abstract = "Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are
   important intestinal neurotransmitters that coexist in the gut enteric
   nervous system and play an important role in intestinal physiology
   (e.g., absorption, motility, fluid secretion and smooth muscle
   relaxation). It is also known that cold exposure alters several aspects
   of gastrointestinal physiology and induces hyperphagia to meet increased
   metabolic demands, but there are no data regarding NO and VIP
   involvement in intestinal response during acclimation to cold. The
   objective of this study was to determine the influence of long-term
   l-arginine supplementation on the expression of the three isoforms of
   nitric oxide synthase (NOS) and VIP in small intestine of rats
   acclimated to room temperature or cold.
   Animals (six per group) acclimated to room temperature (22 +/- A 1 A
   degrees C) and cold (4 +/- A 1 A degrees C), respectively, were treated
   with 2.25 \% l-arginine, a substrate for NOSs, or with 0.01 \% N
   (omega)-nitro-l-arginine methyl ester, an inhibitor of NOSs, for 45
   days. The topographical distribution of VIP and NOSs expression in small
   intestine was studied by immunohistochemistry, and ImageJ software was
   used for semiquantitative densitometric analysis of their
   immunoexpression.
   Long-term dietary l-arginine supplementation increases VIP and NOSs
   immunoexpression at room temperature while at cold increases the
   endothelial NOS, inducible NOS and VIP but decrease neuronal NOS in rat
   small intestine.
   Our results demonstrate that long-term dietary l-arginine
   supplementation modulates NOSs and VIP immunoexpression in rat small
   intestine with respect to ambient temperature, pointing out the eNOS as
   a predominant NOS isoform with an immunoexpression pattern similar to
   VIP.",
journal = "European Journal of Nutrition",
title = "Long-term dietary L-arginine supplementation increases endothelial
 nitric oxide synthase and vasoactive intestinal peptide immunoexpression
 in rat small intestine",
number = "3",
volume = "53",
doi = "10.1007/s00394-013-0585-8",
pages = "813-821"
}

Velickovic, K., Markelic, M., Golic, I., Otašević, V., Stančić, A., Janković, A., Vucetic, M., Buzadžić, B. J., Korać, B.,& Korac, A.. (2014). Long-term dietary L-arginine supplementation increases endothelial
 nitric oxide synthase and vasoactive intestinal peptide immunoexpression
 in rat small intestine. in European Journal of Nutrition, 53(3), 813-821.
https://doi.org/10.1007/s00394-013-0585-8

Velickovic K, Markelic M, Golic I, Otašević V, Stančić A, Janković A, Vucetic M, Buzadžić BJ, Korać B, Korac A. Long-term dietary L-arginine supplementation increases endothelial
 nitric oxide synthase and vasoactive intestinal peptide immunoexpression
 in rat small intestine. in European Journal of Nutrition. 2014;53(3):813-821.
doi:10.1007/s00394-013-0585-8 .

Velickovic, Ksenija, Markelic, Milica, Golic, Igor, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Vucetic, Milica, Buzadžić, Biljana J., Korać, Bato, Korac, Aleksandra, "Long-term dietary L-arginine supplementation increases endothelial
 nitric oxide synthase and vasoactive intestinal peptide immunoexpression
 in rat small intestine" in European Journal of Nutrition, 53, no. 3 (2014):813-821,
https://doi.org/10.1007/s00394-013-0585-8 . .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Korac, Aleksandra
AU  - Srdic-Galic, Biljana
AU  - Buzadžić, Biljana J.
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Vucetic, Milica
AU  - Markelic, Milica
AU  - Velickovic, Ksenija
AU  - Golic, Igor
AU  - Korać, Bato
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2220
AB  - Objective. Metabolic homeostasis depends on adipocyte metabolic
   responses/processes, most of which are redox-regulated. Besides,
   visceral and subcutaneous adipose tissues (VAT and SAT, respectively)
   differ metabolically and in their contribution to metabolic
   complications, but their redox characteristics in humans are still
   unknown. To understand the molecular mechanisms of metabolic syndrome
   development, we analysed the redox characteristics of VAT and SAT in
   groups with various body weights and metabolic risks.
   Material and Methods. Fifty premenopausal women were classified
   according to body mass index into normal-weight and obese groups, and
   these groups were further sub-classified into metabolically healthy and
   metabolically obese ({''}at risk{''}) based on the homeostasis model
   assessment of insulin resistance (HOMA-IR) index and the triglyceride,
   total-, LDL- and HDL-cholesterol levels. Antioxidant components, NADPH
   oxidase protein and 4-hydroxynonenal (4-HNE) levels were analysed in VAT
   and SAT.
   Results. Compared with the SAT, the VAT showed a higher basal level of
   glutathione (GSH) and GSH-dependent enzyme activities. Compared with the
   metabolically healthy normal-weight controls, the obese groups of women
   showed lower GSH levels in both depots. However, in these groups,
   additional prooxidative changes (increased NADPH oxidase and 4-HNE and
   decreased levels of SOD and/or CAT) were observed only in VAT.
   Conclusions. Because of the critical role of thiol-redox homeostasis in
   lipogenesis, interdepot-differences in the GSH-dependent antioxidant
   part may be connected to the higher metabolic activity found in VAT.
   Analogously, the lower GSH levels that occur during obesity and the
   corresponding additional redox imbalance may be signs of VAT metabolic
   dysfunction that underlie the subsequent metabolic impairment. (C) 2014
   Elsevier Inc. All rights reserved.
T2  - Metabolism-Clinical and Experimental
T1  - Differences in the redox status of human visceral and subcutaneous
 adipose tissues - relationships to obesity and metabolic risk
IS  - 5
VL  - 63
DO  - 10.1016/j.metabol.2014.01.009
SP  - 661
EP  - 671
ER  - 

@article{
author = "Janković, Aleksandra and Korac, Aleksandra and Srdic-Galic, Biljana and Buzadžić, Biljana J. and Otašević, Vesna and Stančić, Ana and Vucetic, Milica and Markelic, Milica and Velickovic, Ksenija and Golic, Igor and Korać, Bato",
year = "2014",
abstract = "Objective. Metabolic homeostasis depends on adipocyte metabolic
   responses/processes, most of which are redox-regulated. Besides,
   visceral and subcutaneous adipose tissues (VAT and SAT, respectively)
   differ metabolically and in their contribution to metabolic
   complications, but their redox characteristics in humans are still
   unknown. To understand the molecular mechanisms of metabolic syndrome
   development, we analysed the redox characteristics of VAT and SAT in
   groups with various body weights and metabolic risks.
   Material and Methods. Fifty premenopausal women were classified
   according to body mass index into normal-weight and obese groups, and
   these groups were further sub-classified into metabolically healthy and
   metabolically obese ({''}at risk{''}) based on the homeostasis model
   assessment of insulin resistance (HOMA-IR) index and the triglyceride,
   total-, LDL- and HDL-cholesterol levels. Antioxidant components, NADPH
   oxidase protein and 4-hydroxynonenal (4-HNE) levels were analysed in VAT
   and SAT.
   Results. Compared with the SAT, the VAT showed a higher basal level of
   glutathione (GSH) and GSH-dependent enzyme activities. Compared with the
   metabolically healthy normal-weight controls, the obese groups of women
   showed lower GSH levels in both depots. However, in these groups,
   additional prooxidative changes (increased NADPH oxidase and 4-HNE and
   decreased levels of SOD and/or CAT) were observed only in VAT.
   Conclusions. Because of the critical role of thiol-redox homeostasis in
   lipogenesis, interdepot-differences in the GSH-dependent antioxidant
   part may be connected to the higher metabolic activity found in VAT.
   Analogously, the lower GSH levels that occur during obesity and the
   corresponding additional redox imbalance may be signs of VAT metabolic
   dysfunction that underlie the subsequent metabolic impairment. (C) 2014
   Elsevier Inc. All rights reserved.",
journal = "Metabolism-Clinical and Experimental",
title = "Differences in the redox status of human visceral and subcutaneous
 adipose tissues - relationships to obesity and metabolic risk",
number = "5",
volume = "63",
doi = "10.1016/j.metabol.2014.01.009",
pages = "661-671"
}

Janković, A., Korac, A., Srdic-Galic, B., Buzadžić, B. J., Otašević, V., Stančić, A., Vucetic, M., Markelic, M., Velickovic, K., Golic, I.,& Korać, B.. (2014). Differences in the redox status of human visceral and subcutaneous
 adipose tissues - relationships to obesity and metabolic risk. in Metabolism-Clinical and Experimental, 63(5), 661-671.
https://doi.org/10.1016/j.metabol.2014.01.009

Janković A, Korac A, Srdic-Galic B, Buzadžić BJ, Otašević V, Stančić A, Vucetic M, Markelic M, Velickovic K, Golic I, Korać B. Differences in the redox status of human visceral and subcutaneous
 adipose tissues - relationships to obesity and metabolic risk. in Metabolism-Clinical and Experimental. 2014;63(5):661-671.
doi:10.1016/j.metabol.2014.01.009 .

Janković, Aleksandra, Korac, Aleksandra, Srdic-Galic, Biljana, Buzadžić, Biljana J., Otašević, Vesna, Stančić, Ana, Vucetic, Milica, Markelic, Milica, Velickovic, Ksenija, Golic, Igor, Korać, Bato, "Differences in the redox status of human visceral and subcutaneous
 adipose tissues - relationships to obesity and metabolic risk" in Metabolism-Clinical and Experimental, 63, no. 5 (2014):661-671,
https://doi.org/10.1016/j.metabol.2014.01.009 . .