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  - JOUR
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Bovan, Dijana
AU  - Jelača, Sanja
AU  - Jović, Zorana
AU  - Purić, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5470
AB  - In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo
IS  - 3
VL  - 13
DO  - 10.3390/nano13030372
SP  - 372
ER  - 

@article{
author = "Markelić, Milica and Mojić, Marija and Bovan, Dijana and Jelača, Sanja and Jović, Zorana and Purić, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo",
number = "3",
volume = "13",
doi = "10.3390/nano13030372",
pages = "372"
}

Markelić, M., Mojić, M., Bovan, D., Jelača, S., Jović, Z., Purić, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials
Basel: MDPI., 13(3), 372.
https://doi.org/10.3390/nano13030372

Markelić M, Mojić M, Bovan D, Jelača S, Jović Z, Purić M, Koruga D, Mijatović S, Maksimović-Ivanić D. Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials. 2023;13(3):372.
doi:10.3390/nano13030372 .

Markelić, Milica, Mojić, Marija, Bovan, Dijana, Jelača, Sanja, Jović, Zorana, Purić, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo" in Nanomaterials, 13, no. 3 (2023):372,
https://doi.org/10.3390/nano13030372 . .

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  - JOUR
AU  - Markelić, Milica
AU  - Drača, Dijana
AU  - Krajnović, Tamara
AU  - Jović, Zorana
AU  - Vuksanović, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4953
AB  - (1) Background: Their unique structure and electron deficiency have brought fullerenes
into the focus of research in many fields, including medicine. The hyper-harmonized hydroxylated
fullerene water complex (3HFWC) formulation has solved the limitations of the poor solubility
and bioavailability of fullerenes. To achieve better antitumor activity, 3HFWC was combined with
short-term irradiation of cells with hyperpolarized light (HPL) generated by the application of a
nanophotonic fullerene filter in a Bioptron® device. The benefits of HPL were confirmed in the
microcirculation, wound healing and immunological function. (2) Methods: B16, B16-F10 and A375
melanoma cells were exposed to a wide spectrum of 3HFWC doses and to a single short-term HPL
irradiation. (3) Results: Apart from the differences in the redox status and level of invasiveness, the
effects of the treatments were quite similar. Decreased viability, morphological alteration, signs of
melanocytic differentiation and cellular senescence were observed upon the successful internalization
of the nanoquantum substance. (4) Conclusions: Overall, 3HFWC/HPL promoted melanoma cell
reprogramming toward a normal phenotype.
PB  - Basel: MDPI
T2  - Nanomaterials (Basel)
T1  - Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro
IS  - 8
VL  - 12
DO  - 10.3390/nano12081331
SP  - 1331
ER  - 

@article{
author = "Markelić, Milica and Drača, Dijana and Krajnović, Tamara and Jović, Zorana and Vuksanović, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "(1) Background: Their unique structure and electron deficiency have brought fullerenes
into the focus of research in many fields, including medicine. The hyper-harmonized hydroxylated
fullerene water complex (3HFWC) formulation has solved the limitations of the poor solubility
and bioavailability of fullerenes. To achieve better antitumor activity, 3HFWC was combined with
short-term irradiation of cells with hyperpolarized light (HPL) generated by the application of a
nanophotonic fullerene filter in a Bioptron® device. The benefits of HPL were confirmed in the
microcirculation, wound healing and immunological function. (2) Methods: B16, B16-F10 and A375
melanoma cells were exposed to a wide spectrum of 3HFWC doses and to a single short-term HPL
irradiation. (3) Results: Apart from the differences in the redox status and level of invasiveness, the
effects of the treatments were quite similar. Decreased viability, morphological alteration, signs of
melanocytic differentiation and cellular senescence were observed upon the successful internalization
of the nanoquantum substance. (4) Conclusions: Overall, 3HFWC/HPL promoted melanoma cell
reprogramming toward a normal phenotype.",
publisher = "Basel: MDPI",
journal = "Nanomaterials (Basel)",
title = "Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro",
number = "8",
volume = "12",
doi = "10.3390/nano12081331",
pages = "1331"
}

Markelić, M., Drača, D., Krajnović, T., Jović, Z., Vuksanović, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro. in Nanomaterials (Basel)
Basel: MDPI., 12(8), 1331.
https://doi.org/10.3390/nano12081331

Markelić M, Drača D, Krajnović T, Jović Z, Vuksanović M, Koruga D, Mijatović S, Maksimović-Ivanić D. Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro. in Nanomaterials (Basel). 2022;12(8):1331.
doi:10.3390/nano12081331 .

Markelić, Milica, Drača, Dijana, Krajnović, Tamara, Jović, Zorana, Vuksanović, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro" in Nanomaterials (Basel), 12, no. 8 (2022):1331,
https://doi.org/10.3390/nano12081331 . .

TY  - CONF
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Drača, Dijana
AU  - Jelača, Sanja
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5285
AB  - Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5285
ER  - 

@conference{
author = "Markelić, Milica and Mojić, Marija and Drača, Dijana and Jelača, Sanja and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5285"
}

Markelić, M., Mojić, M., Drača, D., Jelača, S., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_5285

Markelić M, Mojić M, Drača D, Jelača S, Koruga D, Mijatović S, Maksimović-Ivanić D. Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_5285 .

Markelić, Milica, Mojić, Marija, Drača, Dijana, Jelača, Sanja, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):95,
https://hdl.handle.net/21.15107/rcub_ibiss_5285 .

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  - CONF
AU  - Drača, Dijana
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Jović, Zorana
AU  - Dragičević, Aleksandra
AU  - Koruga, Đuro
AU  - Maksimović-Ivanić, Danijela
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4433
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
AB  - Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features are not adequately studied. In this study, we aim to display the characteristics 
of PGA. 116 non‐smoker adult asthma patients (80% female, mean age 39± 12.9) admitted to three tertiary centres were included. Their demographic and clinical features, allergy 
status, biochemical results, Asthma Control Test (ACT) scores, spirometry and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. 
According to induced sputum cell counts, four phenotypes were detected: eosinophilic (EA) (22.4%), mixed (MGA) (6.9%), neutrophilic (NA) (7.8%) and paucigranulocytic (62.9%). In 
sputum, macrophages were higher in the PGA group compared to other groups (PGA vs NA and PGA vs MGA: p<0.001, PGA vs EA: p=0.03). The atopy rate between phenotypes was 
the same. Although forced expiratory flow 1st second (FEV1) was similar in four groups, FEV1/FVC was higher (p=0.013) and FEV1 reversibility was lower in PGA patients than the 
corresponding values in other phenotypes (p=0.015). Low reversibility was comparable in both inhaled corticosteroid naive PGA patients and in those on ICS treatment. Although 
insignificant, FeNO and blood eosinophil counts were higher in MGA and EA groups while these were the lowest in the PGA group. Uncontrolled asthma ratio was low in PGA (16%) 
while it was 11% for NA, 25% for MG and 23% in EA. Macrophages are predominant in sputum of PGA patients. Besides lower uncontrolled asthma ratio, lower FEV1 reversibility is 
a prominent characteristic of this phenotype.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Anti‐melanoma effects of Hyper‐harmonized hydroxylated fullerene water complex and hyperpolarized light in vivo
IS  - Suppl 1
VL  - 51
DO  - 10.1002/eji.202170200
SP  - 353
ER  - 

@conference{
author = "Drača, Dijana and Markelić, Milica and Mojić, Marija and Jelača, Sanja and Mijatović, Sanja and Jović, Zorana and Dragičević, Aleksandra and Koruga, Đuro and Maksimović-Ivanić, Danijela",
year = "2021",
abstract = "Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features are not adequately studied. In this study, we aim to display the characteristics 
of PGA. 116 non‐smoker adult asthma patients (80% female, mean age 39± 12.9) admitted to three tertiary centres were included. Their demographic and clinical features, allergy 
status, biochemical results, Asthma Control Test (ACT) scores, spirometry and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. 
According to induced sputum cell counts, four phenotypes were detected: eosinophilic (EA) (22.4%), mixed (MGA) (6.9%), neutrophilic (NA) (7.8%) and paucigranulocytic (62.9%). In 
sputum, macrophages were higher in the PGA group compared to other groups (PGA vs NA and PGA vs MGA: p<0.001, PGA vs EA: p=0.03). The atopy rate between phenotypes was 
the same. Although forced expiratory flow 1st second (FEV1) was similar in four groups, FEV1/FVC was higher (p=0.013) and FEV1 reversibility was lower in PGA patients than the 
corresponding values in other phenotypes (p=0.015). Low reversibility was comparable in both inhaled corticosteroid naive PGA patients and in those on ICS treatment. Although 
insignificant, FeNO and blood eosinophil counts were higher in MGA and EA groups while these were the lowest in the PGA group. Uncontrolled asthma ratio was low in PGA (16%) 
while it was 11% for NA, 25% for MG and 23% in EA. Macrophages are predominant in sputum of PGA patients. Besides lower uncontrolled asthma ratio, lower FEV1 reversibility is 
a prominent characteristic of this phenotype.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Anti‐melanoma effects of Hyper‐harmonized hydroxylated fullerene water complex and hyperpolarized light in vivo",
number = "Suppl 1",
volume = "51",
doi = "10.1002/eji.202170200",
pages = "353"
}

Drača, D., Markelić, M., Mojić, M., Jelača, S., Mijatović, S., Jović, Z., Dragičević, A., Koruga, Đ.,& Maksimović-Ivanić, D.. (2021). Anti‐melanoma effects of Hyper‐harmonized hydroxylated fullerene water complex and hyperpolarized light in vivo. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 51(Suppl 1), 353.
https://doi.org/10.1002/eji.202170200

Drača D, Markelić M, Mojić M, Jelača S, Mijatović S, Jović Z, Dragičević A, Koruga Đ, Maksimović-Ivanić D. Anti‐melanoma effects of Hyper‐harmonized hydroxylated fullerene water complex and hyperpolarized light in vivo. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;51(Suppl 1):353.
doi:10.1002/eji.202170200 .

Drača, Dijana, Markelić, Milica, Mojić, Marija, Jelača, Sanja, Mijatović, Sanja, Jović, Zorana, Dragičević, Aleksandra, Koruga, Đuro, Maksimović-Ivanić, Danijela, "Anti‐melanoma effects of Hyper‐harmonized hydroxylated fullerene water complex and hyperpolarized light in vivo" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting, 51, no. Suppl 1 (2021):353,
https://doi.org/10.1002/eji.202170200 . .

TY  - JOUR
AU  - Dakić, Tamara B.
AU  - Jevđović, Tanja V.
AU  - Perić, Mina I.
AU  - Bjelobaba, Ivana
AU  - Markelić, Milica B.
AU  - Milutinović, Bojana S.
AU  - Lakić, Iva V.
AU  - Jasnić, Nebojša I.
AU  - Đorđević, Jelena D.
AU  - Vujović, Predrag Z.
PY  - 2017
UR  - http://doi.wiley.com/10.1111/ejn.13607
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2779
AB  - In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular.
T2  - European Journal of Neuroscience
T1  - Short-term fasting promotes insulin expression in rat hypothalamus
IS  - 1
VL  - 46
DO  - 10.1111/ejn.13607
SP  - 1730
EP  - 1737
ER  - 

@article{
author = "Dakić, Tamara B. and Jevđović, Tanja V. and Perić, Mina I. and Bjelobaba, Ivana and Markelić, Milica B. and Milutinović, Bojana S. and Lakić, Iva V. and Jasnić, Nebojša I. and Đorđević, Jelena D. and Vujović, Predrag Z.",
year = "2017",
abstract = "In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular.",
journal = "European Journal of Neuroscience",
title = "Short-term fasting promotes insulin expression in rat hypothalamus",
number = "1",
volume = "46",
doi = "10.1111/ejn.13607",
pages = "1730-1737"
}

Dakić, T. B., Jevđović, T. V., Perić, M. I., Bjelobaba, I., Markelić, M. B., Milutinović, B. S., Lakić, I. V., Jasnić, N. I., Đorđević, J. D.,& Vujović, P. Z.. (2017). Short-term fasting promotes insulin expression in rat hypothalamus. in European Journal of Neuroscience, 46(1), 1730-1737.
https://doi.org/10.1111/ejn.13607

Dakić TB, Jevđović TV, Perić MI, Bjelobaba I, Markelić MB, Milutinović BS, Lakić IV, Jasnić NI, Đorđević JD, Vujović PZ. Short-term fasting promotes insulin expression in rat hypothalamus. in European Journal of Neuroscience. 2017;46(1):1730-1737.
doi:10.1111/ejn.13607 .

Dakić, Tamara B., Jevđović, Tanja V., Perić, Mina I., Bjelobaba, Ivana, Markelić, Milica B., Milutinović, Bojana S., Lakić, Iva V., Jasnić, Nebojša I., Đorđević, Jelena D., Vujović, Predrag Z., "Short-term fasting promotes insulin expression in rat hypothalamus" in European Journal of Neuroscience, 46, no. 1 (2017):1730-1737,
https://doi.org/10.1111/ejn.13607 . .

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 . .