TY  - JOUR
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Savić, Nevena
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4910
AB  - The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.
PB  - London:Hindawi
T2  - Oxidative Medicine and Cellular Longevity
T1  - Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions
VL  - 2022
DO  - 10.1155/2022/3873420
SP  - 3873420
ER  - 

@article{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Veličković, Ksenija and Savić, Nevena and Otašević, Vesna",
year = "2022",
abstract = "The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.",
publisher = "London:Hindawi",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions",
volume = "2022",
doi = "10.1155/2022/3873420",
pages = "3873420"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Mićanović, D., Ivanović, A., Veličković, K., Savić, N.,& Otašević, V.. (2022). Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity
London:Hindawi., 2022, 3873420.
https://doi.org/10.1155/2022/3873420

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Mićanović D, Ivanović A, Veličković K, Savić N, Otašević V. Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity. 2022;2022:3873420.
doi:10.1155/2022/3873420 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Veličković, Ksenija, Savić, Nevena, Otašević, Vesna, "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions" in Oxidative Medicine and Cellular Longevity, 2022 (2022):3873420,
https://doi.org/10.1155/2022/3873420 . .

TY  - CONF
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Veličković, Ksenija
AU  - Grigorov, Ilijana
AU  - Stančić, Ana
PY  - 2022
UR  - uri:https://meetings.embo.org/event/22-thiol-oxidation
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5265
AB  - The key pathological event in the development of diabetes is the loss of functional β-cells. We examined here so far unknown the contribution of ferroptosis to β-cell death in diabetic conditions in vivo and in vitro. Thus, male C57BL/6 mice were divided into three groups: diabetic, (strepozotocin-treated 40 mg/kg/5 days), diabetic+ferrostatin-1-treated (Fer-1, 1 mg/kg from day 1-21) and control, while Rin-5F were treated with diabetes-mimicking factors: high glucose (25mM), hydrogen peroxide (75 μM), or streptozotocin (10mM) for 12h. In diabetic mice a significant increase in macrophage infiltration and lipid peroxide accumulation in pancreatic islets, followed by a decrease in an insulin-positive cell population, expression of GPX4, cysteine/glutamate transporter xCT and heme oxygenase 1 were observed. Applied diabetes-mimicking conditions increased death of Rin-5f β-cells, accumulation of reactive oxygen species, lipid peroxides and iron along with a decrease in the activation of transcription factor Nrf2, expression of GPX4 and mitochondrial membrane potential. The use of ferroptosis inhibitor, Fer-1, completely reversed examined ferroptosis-related changes, i.e. had positive effects on both pancreatic islets of diabetic animals and in vitro β-cells. These results show that modulation, i.e. inhibition of ferroptosis in diabetes may be a promising new approach to conserving β-cell populations and treating diabetes.
PB  - Heidelberg: European Molecular Biology Organization (EMBO)
C3  - EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13
T1  - Inhibition of ferroptosis increases the survival of β-cells
SP  - 52
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5265
ER  - 

@conference{
author = "Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Veličković, Ksenija and Grigorov, Ilijana and Stančić, Ana",
year = "2022",
abstract = "The key pathological event in the development of diabetes is the loss of functional β-cells. We examined here so far unknown the contribution of ferroptosis to β-cell death in diabetic conditions in vivo and in vitro. Thus, male C57BL/6 mice were divided into three groups: diabetic, (strepozotocin-treated 40 mg/kg/5 days), diabetic+ferrostatin-1-treated (Fer-1, 1 mg/kg from day 1-21) and control, while Rin-5F were treated with diabetes-mimicking factors: high glucose (25mM), hydrogen peroxide (75 μM), or streptozotocin (10mM) for 12h. In diabetic mice a significant increase in macrophage infiltration and lipid peroxide accumulation in pancreatic islets, followed by a decrease in an insulin-positive cell population, expression of GPX4, cysteine/glutamate transporter xCT and heme oxygenase 1 were observed. Applied diabetes-mimicking conditions increased death of Rin-5f β-cells, accumulation of reactive oxygen species, lipid peroxides and iron along with a decrease in the activation of transcription factor Nrf2, expression of GPX4 and mitochondrial membrane potential. The use of ferroptosis inhibitor, Fer-1, completely reversed examined ferroptosis-related changes, i.e. had positive effects on both pancreatic islets of diabetic animals and in vitro β-cells. These results show that modulation, i.e. inhibition of ferroptosis in diabetes may be a promising new approach to conserving β-cell populations and treating diabetes.",
publisher = "Heidelberg: European Molecular Biology Organization (EMBO)",
journal = "EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13",
title = "Inhibition of ferroptosis increases the survival of β-cells",
pages = "52",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5265"
}

Otašević, V., Saksida, T., Markelić, M., Veličković, K., Grigorov, I.,& Stančić, A.. (2022). Inhibition of ferroptosis increases the survival of β-cells. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13
Heidelberg: European Molecular Biology Organization (EMBO)., 52.
https://hdl.handle.net/21.15107/rcub_ibiss_5265

Otašević V, Saksida T, Markelić M, Veličković K, Grigorov I, Stančić A. Inhibition of ferroptosis increases the survival of β-cells. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13. 2022;:52.
https://hdl.handle.net/21.15107/rcub_ibiss_5265 .

Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Veličković, Ksenija, Grigorov, Ilijana, Stančić, Ana, "Inhibition of ferroptosis increases the survival of β-cells" in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13 (2022):52,
https://hdl.handle.net/21.15107/rcub_ibiss_5265 .

TY  - CONF
AU  - Vučetić, Milica
AU  - Markelić, Milica
AU  - Janković, Aleksandra
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Korać, Aleksandra
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1910
AB  - Natural hypothermia, in addition to allowing energy saving in hostile conditions, has been associated with delayed aging and increased longevity. However, the molecular basis responsible for observed correlations between the use of daily torpor/hibernation and indices of rate of aging is hitherto unclear. Considering central role of mitochondria dysfunction in the ageing process, we examined several mechanisms that might be involved in mitochondrial protection against oxidative damage during euthermia-hypothermia (and vice versa) transition, in brown adipose tissue (BAT) of the European Ground Squirrel (Spermophilus citellus).

Results showed that in hibernation increased protein expression of Mn superoxide dismutase coincides with decreased content of ATP synthase and uncoupling protein 1. This suggests that BAT mitochondria during hibernation are protected from oxidative injuries by suppressed oxidative capacity, as well as by upregulated antioxidant defense. Also, the data indicate that such molecular pattern of changes is initiated already during prehibernating period. Namely, in this period we observed accumulations of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor (erythroid 2-related)-like 2, which are probably responsible for suppressed oxidative metabolism, i.e. increased antioxidant capacity, respectively. Increased expression of the mitofusin 1 and detection of the megamitochondria in the prehibernating period indicate intensive mitofusion process in the BAT. This may be another mechanism of protection of mitochondrial content/function during euthermia-hypothermia transition.

The results of the study suggest mechanisms that might be associated with increased resistance of “hibernating” mitochondria to the oxidative damage. Also, the data showed that biochemistry responsible for redox balance within the cell involves integration of antioxidant response and transcription control of overall metabolism. Finally, the results go in favor of the previous reports that suggested HIF-1 as a negative modulator of aging.
PB  - Elsevier
C3  - SFRR-E/SNFS Conference Abstracts; 2015 Sep 1-4; Stuttgart, Germany
T1  - Molecular mechanisms of mitochondrial protection against oxidative
 damage in hibernators - the anti-aging effects of heterothermy
IS  - 1
VL  - 86
DO  - 10.1016/j.freeradbiomed.2015.07.028
ER  - 

@conference{
author = "Vučetić, Milica and Markelić, Milica and Janković, Aleksandra and Stančić, Ana and Otašević, Vesna and Korać, Aleksandra and Buzadžić, Biljana J. and Korać, Bato",
year = "2015",
abstract = "Natural hypothermia, in addition to allowing energy saving in hostile conditions, has been associated with delayed aging and increased longevity. However, the molecular basis responsible for observed correlations between the use of daily torpor/hibernation and indices of rate of aging is hitherto unclear. Considering central role of mitochondria dysfunction in the ageing process, we examined several mechanisms that might be involved in mitochondrial protection against oxidative damage during euthermia-hypothermia (and vice versa) transition, in brown adipose tissue (BAT) of the European Ground Squirrel (Spermophilus citellus).

Results showed that in hibernation increased protein expression of Mn superoxide dismutase coincides with decreased content of ATP synthase and uncoupling protein 1. This suggests that BAT mitochondria during hibernation are protected from oxidative injuries by suppressed oxidative capacity, as well as by upregulated antioxidant defense. Also, the data indicate that such molecular pattern of changes is initiated already during prehibernating period. Namely, in this period we observed accumulations of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor (erythroid 2-related)-like 2, which are probably responsible for suppressed oxidative metabolism, i.e. increased antioxidant capacity, respectively. Increased expression of the mitofusin 1 and detection of the megamitochondria in the prehibernating period indicate intensive mitofusion process in the BAT. This may be another mechanism of protection of mitochondrial content/function during euthermia-hypothermia transition.

The results of the study suggest mechanisms that might be associated with increased resistance of “hibernating” mitochondria to the oxidative damage. Also, the data showed that biochemistry responsible for redox balance within the cell involves integration of antioxidant response and transcription control of overall metabolism. Finally, the results go in favor of the previous reports that suggested HIF-1 as a negative modulator of aging.",
publisher = "Elsevier",
journal = "SFRR-E/SNFS Conference Abstracts; 2015 Sep 1-4; Stuttgart, Germany",
title = "Molecular mechanisms of mitochondrial protection against oxidative
 damage in hibernators - the anti-aging effects of heterothermy",
number = "1",
volume = "86",
doi = "10.1016/j.freeradbiomed.2015.07.028"
}

Vučetić, M., Markelić, M., Janković, A., Stančić, A., Otašević, V., Korać, A., Buzadžić, B. J.,& Korać, B.. (2015). Molecular mechanisms of mitochondrial protection against oxidative
 damage in hibernators - the anti-aging effects of heterothermy. in SFRR-E/SNFS Conference Abstracts; 2015 Sep 1-4; Stuttgart, Germany
Elsevier., 86(1).
https://doi.org/10.1016/j.freeradbiomed.2015.07.028

Vučetić M, Markelić M, Janković A, Stančić A, Otašević V, Korać A, Buzadžić BJ, Korać B. Molecular mechanisms of mitochondrial protection against oxidative
 damage in hibernators - the anti-aging effects of heterothermy. in SFRR-E/SNFS Conference Abstracts; 2015 Sep 1-4; Stuttgart, Germany. 2015;86(1).
doi:10.1016/j.freeradbiomed.2015.07.028 .

Vučetić, Milica, Markelić, Milica, Janković, Aleksandra, Stančić, Ana, Otašević, Vesna, Korać, Aleksandra, Buzadžić, Biljana J., Korać, Bato, "Molecular mechanisms of mitochondrial protection against oxidative
 damage in hibernators - the anti-aging effects of heterothermy" in SFRR-E/SNFS Conference Abstracts; 2015 Sep 1-4; Stuttgart, Germany, 86, no. 1 (2015),
https://doi.org/10.1016/j.freeradbiomed.2015.07.028 . .

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Golic, Igor
AU  - Markelic, Milica
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra
AU  - Korać, Bato
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1921
AB  - Conversion of white into brown adipose tissue may have important
   implications in obesity resistance and treatment. Several browning
   agents or conditions ignite thermogenesis in white adipose tissue (WAT).
   To reveal the capacity of WAT to function in a brownish/burning mode
   over the long term, we investigated the progression of the rat
   retroperitoneal WAT (rpWAT) browning during 45days of cold acclimation.
   During the early stages of cold acclimation, the majority of rpWAT
   adipocytes underwent multilocularization and thermogenic-profile
   induction, as demonstrated by the presence of a multitude of uncoupling
   protein 1 (UCP1)-immunopositive paucilocular adipocytes containing
   peroxisome proliferator-activated receptor (PPAR) coactivator-1 (PGC-1)
   and PR domain-containing 16 (PRDM16) in their nuclei. After 45days, all
   adipocytes remained PRDM16 immunopositive, but only a few multilocular
   adipocytes rich in mitochondria remained UCP1/PGC-1 immunopositive.
   Molecular evidence showed that thermogenic recruitment of rpWAT occurred
   following cold exposure, but returned to starting levels after cold
   acclimation. Compared with controls (22 +/- 1 degrees C), levels of UCP1
   mRNA increased in parallel with PPAR (PPAR from days 1 to 7 and PGC-1 on
   day 1). Transcriptional recruitment of rpWAT was followed by an increase
   in UCP1 protein content (from days 1 to 21). Results clearly showed that
   most of the adipocytes within rpWAT underwent transient brown-fat-like
   thermogenic recruitment upon stimulation, but only a minority of cells
   retained a brown adipose tissue-like phenotype after the attainment of
   cold acclimation. Therefore, browning of WAT is dependent on both
   maintaining the thermogenic response and retaining enough brown-like
   thermogenically competent adipocytes in the long-term. Both aspects of
   browning could be important for long-term energy homeostasis and
   body-weight regulation.
T2  - Journal of Physiology-London
T1  - Two key temporally distinguishable molecular and cellular components of
 white adipose tissue browning during cold acclimation
IS  - 15
VL  - 593
DO  - 10.1113/JP270805
SP  - 3267
EP  - 3280
ER  - 

@article{
author = "Janković, Aleksandra and Golic, Igor and Markelic, Milica and Stančić, Ana and Otašević, Vesna and Buzadžić, Biljana J. and Korac, Aleksandra and Korać, Bato",
year = "2015",
abstract = "Conversion of white into brown adipose tissue may have important
   implications in obesity resistance and treatment. Several browning
   agents or conditions ignite thermogenesis in white adipose tissue (WAT).
   To reveal the capacity of WAT to function in a brownish/burning mode
   over the long term, we investigated the progression of the rat
   retroperitoneal WAT (rpWAT) browning during 45days of cold acclimation.
   During the early stages of cold acclimation, the majority of rpWAT
   adipocytes underwent multilocularization and thermogenic-profile
   induction, as demonstrated by the presence of a multitude of uncoupling
   protein 1 (UCP1)-immunopositive paucilocular adipocytes containing
   peroxisome proliferator-activated receptor (PPAR) coactivator-1 (PGC-1)
   and PR domain-containing 16 (PRDM16) in their nuclei. After 45days, all
   adipocytes remained PRDM16 immunopositive, but only a few multilocular
   adipocytes rich in mitochondria remained UCP1/PGC-1 immunopositive.
   Molecular evidence showed that thermogenic recruitment of rpWAT occurred
   following cold exposure, but returned to starting levels after cold
   acclimation. Compared with controls (22 +/- 1 degrees C), levels of UCP1
   mRNA increased in parallel with PPAR (PPAR from days 1 to 7 and PGC-1 on
   day 1). Transcriptional recruitment of rpWAT was followed by an increase
   in UCP1 protein content (from days 1 to 21). Results clearly showed that
   most of the adipocytes within rpWAT underwent transient brown-fat-like
   thermogenic recruitment upon stimulation, but only a minority of cells
   retained a brown adipose tissue-like phenotype after the attainment of
   cold acclimation. Therefore, browning of WAT is dependent on both
   maintaining the thermogenic response and retaining enough brown-like
   thermogenically competent adipocytes in the long-term. Both aspects of
   browning could be important for long-term energy homeostasis and
   body-weight regulation.",
journal = "Journal of Physiology-London",
title = "Two key temporally distinguishable molecular and cellular components of
 white adipose tissue browning during cold acclimation",
number = "15",
volume = "593",
doi = "10.1113/JP270805",
pages = "3267-3280"
}

Janković, A., Golic, I., Markelic, M., Stančić, A., Otašević, V., Buzadžić, B. J., Korac, A.,& Korać, B.. (2015). Two key temporally distinguishable molecular and cellular components of
 white adipose tissue browning during cold acclimation. in Journal of Physiology-London, 593(15), 3267-3280.
https://doi.org/10.1113/JP270805

Janković A, Golic I, Markelic M, Stančić A, Otašević V, Buzadžić BJ, Korac A, Korać B. Two key temporally distinguishable molecular and cellular components of
 white adipose tissue browning during cold acclimation. in Journal of Physiology-London. 2015;593(15):3267-3280.
doi:10.1113/JP270805 .

Janković, Aleksandra, Golic, Igor, Markelic, Milica, Stančić, Ana, Otašević, Vesna, Buzadžić, Biljana J., Korac, Aleksandra, Korać, Bato, "Two key temporally distinguishable molecular and cellular components of
 white adipose tissue browning during cold acclimation" in Journal of Physiology-London, 593, no. 15 (2015):3267-3280,
https://doi.org/10.1113/JP270805 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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