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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - 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  - CONF
AU  - Surlan, L
AU  - Otašević, Vesna
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Vučetić, Milica
AU  - Stanković, V
AU  - Stojnić, J
AU  - Radunović, Nebojsa V
AU  - Tulić, Ivan
AU  - Korać, Bato
AU  - Korac, Aleksandra B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1002
C3  - Human Reproduction
T1  - Exosomes as bioactive messengers in a critical time for preimplantation embryos n an ultrastructural study
IS  - null
VL  - 28
SP  - 69
EP  - 186
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1002
ER  - 

@conference{
author = "Surlan, L and Otašević, Vesna and Velicković, Ksenija D and Golić, Igor and Vučetić, Milica and Stanković, V and Stojnić, J and Radunović, Nebojsa V and Tulić, Ivan and Korać, Bato and Korac, Aleksandra B",
year = "2013",
journal = "Human Reproduction",
title = "Exosomes as bioactive messengers in a critical time for preimplantation embryos n an ultrastructural study",
number = "null",
volume = "28",
pages = "69-186",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1002"
}

Surlan, L., Otašević, V., Velicković, K. D., Golić, I., Vučetić, M., Stanković, V., Stojnić, J., Radunović, N. V., Tulić, I., Korać, B.,& Korac, A. B.. (2013). Exosomes as bioactive messengers in a critical time for preimplantation embryos n an ultrastructural study. in Human Reproduction, 28(null), 69-186.
https://hdl.handle.net/21.15107/rcub_ibiss_1002

Surlan L, Otašević V, Velicković KD, Golić I, Vučetić M, Stanković V, Stojnić J, Radunović NV, Tulić I, Korać B, Korac AB. Exosomes as bioactive messengers in a critical time for preimplantation embryos n an ultrastructural study. in Human Reproduction. 2013;28(null):69-186.
https://hdl.handle.net/21.15107/rcub_ibiss_1002 .

Surlan, L, Otašević, Vesna, Velicković, Ksenija D, Golić, Igor, Vučetić, Milica, Stanković, V, Stojnić, J, Radunović, Nebojsa V, Tulić, Ivan, Korać, Bato, Korac, Aleksandra B, "Exosomes as bioactive messengers in a critical time for preimplantation embryos n an ultrastructural study" in Human Reproduction, 28, no. null (2013):69-186,
https://hdl.handle.net/21.15107/rcub_ibiss_1002 .

TY  - JOUR
AU  - Markelić, Milica B
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Klepal, Waltraud
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
AU  - Korac, Aleksandra B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1030
AB  - The aim of this study was to investigate lipofuscin origin in brown adipocytes of hyperinsulinaemic rats and the possible role of lipid peroxidation and iron in this process. Ultrastructural examination revealed hyperinsulinaemia-induced enhancement in the lipofuscin production, accompanied by an increase of mitochondrial damage in brown adipocytes. Extensive fusions of lipid droplets and mitochondria with lysosomes were also observed. Confocal microscopy showed lipofuscin autofluorescence emission in brown adipose tissue (BAT) after excitation at 488 nm and 633 nm, particularly in the insulin-treated groups. The presence and distribution of lipid peroxidation product, 4-hydroxy-2-nonenal (4-HNE), in brown adipocytes was assessed by immunohistochemical examination revealing its higher content after treatment with insulin. The iron content was quantified by electron dispersive X-ray analysis (EDX) showing its higher content in the hyperinsulinaemic groups. The ultrastucture of the majority of lipofuscin granules suggests their mitochondrial origin, which was additionally confirmed by their co-localization with ATP synthase. In conclusion, our results suggest that increased lipofuscinogenesis in the brown adipocytes of hyperinsulinaemic rats is a consequence of lipid peroxidation, mitochondrial damage and iron accumulation.
T2  - Histology and Histopathology
T1  - The origin of lipofuscin in brown adipocytes of hyperinsulinaemic rats: the role of lipid peroxidation and iron
IS  - 4
VL  - 28
SP  - 435
EP  - 503
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1030
ER  - 

@article{
author = "Markelić, Milica B and Velicković, Ksenija D and Golić, Igor and Klepal, Waltraud and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Vučetić, Milica and Buzadžić, Biljana J. and Korać, Bato and Korac, Aleksandra B",
year = "2013",
abstract = "The aim of this study was to investigate lipofuscin origin in brown adipocytes of hyperinsulinaemic rats and the possible role of lipid peroxidation and iron in this process. Ultrastructural examination revealed hyperinsulinaemia-induced enhancement in the lipofuscin production, accompanied by an increase of mitochondrial damage in brown adipocytes. Extensive fusions of lipid droplets and mitochondria with lysosomes were also observed. Confocal microscopy showed lipofuscin autofluorescence emission in brown adipose tissue (BAT) after excitation at 488 nm and 633 nm, particularly in the insulin-treated groups. The presence and distribution of lipid peroxidation product, 4-hydroxy-2-nonenal (4-HNE), in brown adipocytes was assessed by immunohistochemical examination revealing its higher content after treatment with insulin. The iron content was quantified by electron dispersive X-ray analysis (EDX) showing its higher content in the hyperinsulinaemic groups. The ultrastucture of the majority of lipofuscin granules suggests their mitochondrial origin, which was additionally confirmed by their co-localization with ATP synthase. In conclusion, our results suggest that increased lipofuscinogenesis in the brown adipocytes of hyperinsulinaemic rats is a consequence of lipid peroxidation, mitochondrial damage and iron accumulation.",
journal = "Histology and Histopathology",
title = "The origin of lipofuscin in brown adipocytes of hyperinsulinaemic rats: the role of lipid peroxidation and iron",
number = "4",
volume = "28",
pages = "435-503",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1030"
}

Markelić, M. B., Velicković, K. D., Golić, I., Klepal, W., Otašević, V., Stančić, A., Janković, A., Vučetić, M., Buzadžić, B. J., Korać, B.,& Korac, A. B.. (2013). The origin of lipofuscin in brown adipocytes of hyperinsulinaemic rats: the role of lipid peroxidation and iron. in Histology and Histopathology, 28(4), 435-503.
https://hdl.handle.net/21.15107/rcub_ibiss_1030

Markelić MB, Velicković KD, Golić I, Klepal W, Otašević V, Stančić A, Janković A, Vučetić M, Buzadžić BJ, Korać B, Korac AB. The origin of lipofuscin in brown adipocytes of hyperinsulinaemic rats: the role of lipid peroxidation and iron. in Histology and Histopathology. 2013;28(4):435-503.
https://hdl.handle.net/21.15107/rcub_ibiss_1030 .

Markelić, Milica B, Velicković, Ksenija D, Golić, Igor, Klepal, Waltraud, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Vučetić, Milica, Buzadžić, Biljana J., Korać, Bato, Korac, Aleksandra B, "The origin of lipofuscin in brown adipocytes of hyperinsulinaemic rats: the role of lipid peroxidation and iron" in Histology and Histopathology, 28, no. 4 (2013):435-503,
https://hdl.handle.net/21.15107/rcub_ibiss_1030 .

TY  - JOUR
AU  - Otašević, Vesna
AU  - Korac, Aleksandra B
AU  - Vučetić, Milica
AU  - Macanović, Biljana
AU  - Garalejić, Eliana
AU  - Ivanović-Burmazović, Ivana S
AU  - Filipović, Milos R
AU  - Buzadžić, Biljana J.
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Markelić, Milica B
AU  - Korać, Bato
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1067
AB  - Mitochondria play an important role in sperm cell maturation and function. Here, we examined whether (and how) changes in sperm redox milieu affect the functional status of sperm mitochondria, that is, sperm functionality. Compared with the control, incubation in Tyrode's medium for 3 h, under noncapacitating conditions, decreased sperm motility, the amount of nitric oxide ((NO)-N-center dot), the number of MitoTracker (R) Green FM (MT-G) positive mitochondria, and the expression of complexes I and IV of the mitochondrial respiratory chain. In turn, superoxide dismutase (SOD) mimic (M40403) treatment restored/increased these parameters, as well as the expression of endothelial nitric oxide synthase, manganese SOD, and catalase. These data lead to the hypothesis that M40403 improves mitochondrial functional state and motility of spermatozoa, as well as (NO)-N-center dot might be involved in the observed effects of the mimic. Antioxid. Redox Signal. 18, 170-178.
T2  - Antioxidants & Redox Signaling
T1  - Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?
IS  - 2
VL  - 18
SP  - 23
EP  - 178
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1067
ER  - 

@article{
author = "Otašević, Vesna and Korac, Aleksandra B and Vučetić, Milica and Macanović, Biljana and Garalejić, Eliana and Ivanović-Burmazović, Ivana S and Filipović, Milos R and Buzadžić, Biljana J. and Stančić, Ana and Janković, Aleksandra and Velicković, Ksenija D and Golić, Igor and Markelić, Milica B and Korać, Bato",
year = "2013",
abstract = "Mitochondria play an important role in sperm cell maturation and function. Here, we examined whether (and how) changes in sperm redox milieu affect the functional status of sperm mitochondria, that is, sperm functionality. Compared with the control, incubation in Tyrode's medium for 3 h, under noncapacitating conditions, decreased sperm motility, the amount of nitric oxide ((NO)-N-center dot), the number of MitoTracker (R) Green FM (MT-G) positive mitochondria, and the expression of complexes I and IV of the mitochondrial respiratory chain. In turn, superoxide dismutase (SOD) mimic (M40403) treatment restored/increased these parameters, as well as the expression of endothelial nitric oxide synthase, manganese SOD, and catalase. These data lead to the hypothesis that M40403 improves mitochondrial functional state and motility of spermatozoa, as well as (NO)-N-center dot might be involved in the observed effects of the mimic. Antioxid. Redox Signal. 18, 170-178.",
journal = "Antioxidants & Redox Signaling",
title = "Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?",
number = "2",
volume = "18",
pages = "23-178",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1067"
}

Otašević, V., Korac, A. B., Vučetić, M., Macanović, B., Garalejić, E., Ivanović-Burmazović, I. S., Filipović, M. R., Buzadžić, B. J., Stančić, A., Janković, A., Velicković, K. D., Golić, I., Markelić, M. B.,& Korać, B.. (2013). Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?. in Antioxidants & Redox Signaling, 18(2), 23-178.
https://hdl.handle.net/21.15107/rcub_ibiss_1067

Otašević V, Korac AB, Vučetić M, Macanović B, Garalejić E, Ivanović-Burmazović IS, Filipović MR, Buzadžić BJ, Stančić A, Janković A, Velicković KD, Golić I, Markelić MB, Korać B. Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?. in Antioxidants & Redox Signaling. 2013;18(2):23-178.
https://hdl.handle.net/21.15107/rcub_ibiss_1067 .

Otašević, Vesna, Korac, Aleksandra B, Vučetić, Milica, Macanović, Biljana, Garalejić, Eliana, Ivanović-Burmazović, Ivana S, Filipović, Milos R, Buzadžić, Biljana J., Stančić, Ana, Janković, Aleksandra, Velicković, Ksenija D, Golić, Igor, Markelić, Milica B, Korać, Bato, "Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?" in Antioxidants & Redox Signaling, 18, no. 2 (2013):23-178,
https://hdl.handle.net/21.15107/rcub_ibiss_1067 .

TY  - JOUR
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Ivanović-Burmazović, Ivana S
AU  - Filipović, Milos R
AU  - Korac, Aleksandra B
AU  - Markelić, Milica B
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/960
AB  - Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl-2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level >= 12 mM. Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1 alpha - the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1 alpha to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated. To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl-2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder. (C) 2013 Elsevier Inc. All rights reserved.
T2  - Brain Research Bulletin
T1  - Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic
IS  - null
VL  - 99
SP  - 153
EP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_960
ER  - 

@article{
author = "Stančić, Ana and Otašević, Vesna and Janković, Aleksandra and Vučetić, Milica and Ivanović-Burmazović, Ivana S and Filipović, Milos R and Korac, Aleksandra B and Markelić, Milica B and Velicković, Ksenija D and Golić, Igor and Buzadžić, Biljana J. and Korać, Bato",
year = "2013",
abstract = "Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl-2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level >= 12 mM. Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1 alpha - the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1 alpha to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated. To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl-2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder. (C) 2013 Elsevier Inc. All rights reserved.",
journal = "Brain Research Bulletin",
title = "Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic",
number = "null",
volume = "99",
pages = "153-33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_960"
}

Stančić, A., Otašević, V., Janković, A., Vučetić, M., Ivanović-Burmazović, I. S., Filipović, M. R., Korac, A. B., Markelić, M. B., Velicković, K. D., Golić, I., Buzadžić, B. J.,& Korać, B.. (2013). Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic. in Brain Research Bulletin, 99(null), 153-33.
https://hdl.handle.net/21.15107/rcub_ibiss_960

Stančić A, Otašević V, Janković A, Vučetić M, Ivanović-Burmazović IS, Filipović MR, Korac AB, Markelić MB, Velicković KD, Golić I, Buzadžić BJ, Korać B. Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic. in Brain Research Bulletin. 2013;99(null):153-33.
https://hdl.handle.net/21.15107/rcub_ibiss_960 .

Stančić, Ana, Otašević, Vesna, Janković, Aleksandra, Vučetić, Milica, Ivanović-Burmazović, Ivana S, Filipović, Milos R, Korac, Aleksandra B, Markelić, Milica B, Velicković, Ksenija D, Golić, Igor, Buzadžić, Biljana J., Korać, Bato, "Molecular basis of hippocampal energy metabolism in diabetic rats: The effects of SOD mimic" in Brain Research Bulletin, 99, no. null (2013):153-33,
https://hdl.handle.net/21.15107/rcub_ibiss_960 .

TY  - JOUR
AU  - Stančić, Ana
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra B
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Markelić, Milica B
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Korać, Bato
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/951
AB  - This study examined the molecular basis of energy-related regulatory mechanisms underlying metabolic recruitment of skeletal muscle during cold acclimation and possible involvement of the L-arginine/nitric oxide-producing pathway. Rats exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21 and 45 days were divided into three groups: untreated, L-arginine treated and N-omega-nitro-L-arginine methyl ester (L-NAME) treated. Compared with controls (22 +/- 1 degrees C), there was an initial increase in the protein level of 5'-AMP-activated protein kinase alpha (day 1), followed by an increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) and peroxisome proliferator-activated receptors (PPARs): PPAR alpha and PPAR gamma from day 1 and PPAR delta from day 7 of cold acclimation. Activation of the PGC-1 alpha/PPAR transcription program was accompanied by increased protein expression of the key metabolic enzymes in beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation, with the exceptions in complex I (no changes) and ATP synthase (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels, but increased lactate dehydrogenase activity compared with controls (1-45 days). L-arginine sustained, accelerated and/or intensified cold-induced molecular remodeling throughout cold acclimation. L-NAME exerted phase-dependent effects: similar to L-arginine in early cold acclimation and opposite after prolonged cold exposure (from day 21). It seems that upregulation of the PGC-1 alpha/PPAR transcription program early during cold acclimation triggers the molecular recruitment of skeletal muscle underlying the shift to more oxidative metabolism during prolonged cold acclimation. Our results suggest that nitric oxide has a role in maintaining the skeletal muscle oxidative phenotype in late cold acclimation but question its role early in cold acclimation.
T2  - Journal of Experimental Biology
T1  - Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation
IS  - 22
VL  - 216
SP  - 73
EP  - 4241
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_951
ER  - 

@article{
author = "Stančić, Ana and Buzadžić, Biljana J. and Korac, Aleksandra B and Otašević, Vesna and Janković, Aleksandra and Vučetić, Milica and Markelić, Milica B and Velicković, Ksenija D and Golić, Igor and Korać, Bato",
year = "2013",
abstract = "This study examined the molecular basis of energy-related regulatory mechanisms underlying metabolic recruitment of skeletal muscle during cold acclimation and possible involvement of the L-arginine/nitric oxide-producing pathway. Rats exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21 and 45 days were divided into three groups: untreated, L-arginine treated and N-omega-nitro-L-arginine methyl ester (L-NAME) treated. Compared with controls (22 +/- 1 degrees C), there was an initial increase in the protein level of 5'-AMP-activated protein kinase alpha (day 1), followed by an increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) and peroxisome proliferator-activated receptors (PPARs): PPAR alpha and PPAR gamma from day 1 and PPAR delta from day 7 of cold acclimation. Activation of the PGC-1 alpha/PPAR transcription program was accompanied by increased protein expression of the key metabolic enzymes in beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation, with the exceptions in complex I (no changes) and ATP synthase (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels, but increased lactate dehydrogenase activity compared with controls (1-45 days). L-arginine sustained, accelerated and/or intensified cold-induced molecular remodeling throughout cold acclimation. L-NAME exerted phase-dependent effects: similar to L-arginine in early cold acclimation and opposite after prolonged cold exposure (from day 21). It seems that upregulation of the PGC-1 alpha/PPAR transcription program early during cold acclimation triggers the molecular recruitment of skeletal muscle underlying the shift to more oxidative metabolism during prolonged cold acclimation. Our results suggest that nitric oxide has a role in maintaining the skeletal muscle oxidative phenotype in late cold acclimation but question its role early in cold acclimation.",
journal = "Journal of Experimental Biology",
title = "Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation",
number = "22",
volume = "216",
pages = "73-4241",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_951"
}

Stančić, A., Buzadžić, B. J., Korac, A. B., Otašević, V., Janković, A., Vučetić, M., Markelić, M. B., Velicković, K. D., Golić, I.,& Korać, B.. (2013). Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation. in Journal of Experimental Biology, 216(22), 73-4241.
https://hdl.handle.net/21.15107/rcub_ibiss_951

Stančić A, Buzadžić BJ, Korac AB, Otašević V, Janković A, Vučetić M, Markelić MB, Velicković KD, Golić I, Korać B. Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation. in Journal of Experimental Biology. 2013;216(22):73-4241.
https://hdl.handle.net/21.15107/rcub_ibiss_951 .

Stančić, Ana, Buzadžić, Biljana J., Korac, Aleksandra B, Otašević, Vesna, Janković, Aleksandra, Vučetić, Milica, Markelić, Milica B, Velicković, Ksenija D, Golić, Igor, Korać, Bato, "Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation" in Journal of Experimental Biology, 216, no. 22 (2013):73-4241,
https://hdl.handle.net/21.15107/rcub_ibiss_951 .

TY  - JOUR
AU  - Vučetić, Milica
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Korac, Aleksandra B
AU  - Markelić, Milica B
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Buzadžić, Biljana J.
AU  - Storey, Kenneth B
AU  - Korać, Bato
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/944
AB  - Any alteration in oxidative metabolism is coupled with a corresponding response by an antioxidant defense (AD) in appropriate subcellular compartments. Seasonal hibernators pass through circannual metabolic adaptations that allow them to either maintain euthermy (cold acclimation) or enter winter torpor with body temperature falling to low values. The present study aimed to investigate the corresponding pattern of AD enzyme protein expressions associated with these strategies in the main tissues involved in whole animal energy homeostasis: brown and white adipose tissues (BAT and WAT, respectively), liver, and skeletal muscle. European ground squirrels (Spermophilus citellus) were exposed to low temperature (4 +/- 1 C) and then divided into two groups: (1) animals fell into torpor (hibernating group) and (2) animals stayed active and euthermic for 1, 3, 7, 12, or 21 days (cold-exposed group). We examined the effects of cold acclimation and hibernation on the tissue-dependent protein expression of four enzymes which catalyze the two-step detoxification of superoxide to water: superoxide dismutase 1 and 2 (SOD 1 and 2), catalase (CAT), and glutathione peroxidase (GSH-Px). The results showed that hibernation induced an increase of AD enzyme protein expressions in BAT and skeletal muscle. However, AD enzyme contents in liver were largely unaffected during torpor. Under these conditions, different WAT depots responded by elevating the amounts of specific enzymes, as follows: SOD 1 in retroperitoneal WAT, GSH-Px in gonadal WAT, and CAT in subcutaneous WAT. Similar perturbations of AD enzymes contents were seen in all tissues during cold acclimation, often in a time-dependent manner. It can be concluded that BAT and muscle AD capacity undergo the most dramatic changes during both cold acclimation and hibernation, while liver is relatively unaffected by either condition. Additionally, this study provides a basis for further metabolic study that will illuminate the causes of these tissue-specific AD responses, particularly the novel finding of distinct responses by different WAT depots in hibernators. (C) 2013 Elsevier Inc. All rights reserved.
T2  - Free Radical Biology and Medicine
T1  - The impact of cold acclimation and hibernation on antioxidant defenses in the ground squirrel (Spermophilus citellus): An update
IS  - null
VL  - 65
SP  - 47
EP  - 924
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_944
ER  - 

@article{
author = "Vučetić, Milica and Stančić, Ana and Otašević, Vesna and Janković, Aleksandra and Korac, Aleksandra B and Markelić, Milica B and Velicković, Ksenija D and Golić, Igor and Buzadžić, Biljana J. and Storey, Kenneth B and Korać, Bato",
year = "2013",
abstract = "Any alteration in oxidative metabolism is coupled with a corresponding response by an antioxidant defense (AD) in appropriate subcellular compartments. Seasonal hibernators pass through circannual metabolic adaptations that allow them to either maintain euthermy (cold acclimation) or enter winter torpor with body temperature falling to low values. The present study aimed to investigate the corresponding pattern of AD enzyme protein expressions associated with these strategies in the main tissues involved in whole animal energy homeostasis: brown and white adipose tissues (BAT and WAT, respectively), liver, and skeletal muscle. European ground squirrels (Spermophilus citellus) were exposed to low temperature (4 +/- 1 C) and then divided into two groups: (1) animals fell into torpor (hibernating group) and (2) animals stayed active and euthermic for 1, 3, 7, 12, or 21 days (cold-exposed group). We examined the effects of cold acclimation and hibernation on the tissue-dependent protein expression of four enzymes which catalyze the two-step detoxification of superoxide to water: superoxide dismutase 1 and 2 (SOD 1 and 2), catalase (CAT), and glutathione peroxidase (GSH-Px). The results showed that hibernation induced an increase of AD enzyme protein expressions in BAT and skeletal muscle. However, AD enzyme contents in liver were largely unaffected during torpor. Under these conditions, different WAT depots responded by elevating the amounts of specific enzymes, as follows: SOD 1 in retroperitoneal WAT, GSH-Px in gonadal WAT, and CAT in subcutaneous WAT. Similar perturbations of AD enzymes contents were seen in all tissues during cold acclimation, often in a time-dependent manner. It can be concluded that BAT and muscle AD capacity undergo the most dramatic changes during both cold acclimation and hibernation, while liver is relatively unaffected by either condition. Additionally, this study provides a basis for further metabolic study that will illuminate the causes of these tissue-specific AD responses, particularly the novel finding of distinct responses by different WAT depots in hibernators. (C) 2013 Elsevier Inc. All rights reserved.",
journal = "Free Radical Biology and Medicine",
title = "The impact of cold acclimation and hibernation on antioxidant defenses in the ground squirrel (Spermophilus citellus): An update",
number = "null",
volume = "65",
pages = "47-924",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_944"
}

Vučetić, M., Stančić, A., Otašević, V., Janković, A., Korac, A. B., Markelić, M. B., Velicković, K. D., Golić, I., Buzadžić, B. J., Storey, K. B.,& Korać, B.. (2013). The impact of cold acclimation and hibernation on antioxidant defenses in the ground squirrel (Spermophilus citellus): An update. in Free Radical Biology and Medicine, 65(null), 47-924.
https://hdl.handle.net/21.15107/rcub_ibiss_944

Vučetić M, Stančić A, Otašević V, Janković A, Korac AB, Markelić MB, Velicković KD, Golić I, Buzadžić BJ, Storey KB, Korać B. The impact of cold acclimation and hibernation on antioxidant defenses in the ground squirrel (Spermophilus citellus): An update. in Free Radical Biology and Medicine. 2013;65(null):47-924.
https://hdl.handle.net/21.15107/rcub_ibiss_944 .

Vučetić, Milica, Stančić, Ana, Otašević, Vesna, Janković, Aleksandra, Korac, Aleksandra B, Markelić, Milica B, Velicković, Ksenija D, Golić, Igor, Buzadžić, Biljana J., Storey, Kenneth B, Korać, Bato, "The impact of cold acclimation and hibernation on antioxidant defenses in the ground squirrel (Spermophilus citellus): An update" in Free Radical Biology and Medicine, 65, no. null (2013):47-924,
https://hdl.handle.net/21.15107/rcub_ibiss_944 .

TY  - JOUR
AU  - Vučetić, Milica
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Markelić, Milica B
AU  - Golić, Igor
AU  - Velicković, Ksenija D
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra B
AU  - Korać, Bato
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1148
AB  - In this study, the effects of l-arginine-nitric-oxide ((NO)-N-a (TM))-producing pathway on protein content of ubiquitin, as an important component of ubiquitin-proteasome system for protein removal, were investigated. We showed that l-arginine markedly decreased ubiquitin protein content in interscapular brown adipose tissue, both in thermogenic inactive (at room temperature) and thermogenic active (on cold) states; while in l-NAME-treated groups this effect was abolished. This result suggests that nitric oxide ((NO)-N-a (TM)), besides well established roles, is involved in this aspect of structure remodeling, as well.
T2  - Molecular and Cellular Biochemistry
T1  - Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot
IS  - 1-2
VL  - 368
SP  - 503
EP  - 193
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1148
ER  - 

@article{
author = "Vučetić, Milica and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Markelić, Milica B and Golić, Igor and Velicković, Ksenija D and Buzadžić, Biljana J. and Korac, Aleksandra B and Korać, Bato",
year = "2012",
abstract = "In this study, the effects of l-arginine-nitric-oxide ((NO)-N-a (TM))-producing pathway on protein content of ubiquitin, as an important component of ubiquitin-proteasome system for protein removal, were investigated. We showed that l-arginine markedly decreased ubiquitin protein content in interscapular brown adipose tissue, both in thermogenic inactive (at room temperature) and thermogenic active (on cold) states; while in l-NAME-treated groups this effect was abolished. This result suggests that nitric oxide ((NO)-N-a (TM)), besides well established roles, is involved in this aspect of structure remodeling, as well.",
journal = "Molecular and Cellular Biochemistry",
title = "Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot",
number = "1-2",
volume = "368",
pages = "503-193",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1148"
}

Vučetić, M., Otašević, V., Stančić, A., Janković, A., Markelić, M. B., Golić, I., Velicković, K. D., Buzadžić, B. J., Korac, A. B.,& Korać, B.. (2012). Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot. in Molecular and Cellular Biochemistry, 368(1-2), 503-193.
https://hdl.handle.net/21.15107/rcub_ibiss_1148

Vučetić M, Otašević V, Stančić A, Janković A, Markelić MB, Golić I, Velicković KD, Buzadžić BJ, Korac AB, Korać B. Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot. in Molecular and Cellular Biochemistry. 2012;368(1-2):503-193.
https://hdl.handle.net/21.15107/rcub_ibiss_1148 .

Vučetić, Milica, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Markelić, Milica B, Golić, Igor, Velicković, Ksenija D, Buzadžić, Biljana J., Korac, Aleksandra B, Korać, Bato, "Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot" in Molecular and Cellular Biochemistry, 368, no. 1-2 (2012):503-193,
https://hdl.handle.net/21.15107/rcub_ibiss_1148 .

TY  - JOUR
AU  - Jović, Miomir Đ
AU  - Stančić, Ana
AU  - Nenadić, Dragan
AU  - Cekić, Olivera
AU  - Nezić, Dusko G
AU  - Milojević, Predrag S
AU  - Micović, Slobodan V
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra B
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Korać, Bato
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1138
AB  - Background/Aims: Study elucidates and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis. Methods: Twenty-two patients were prospectively randomized in two groups regarding the anesthetic regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac injury and brain natriuretic peptide (BNP) were measured preoperatively and postoperatively. In tissue samples, taken from the interventricular septum, key mitochondrial molecules were determined by Western blot, real time PCR, as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis. Results: The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content was higher in propofol than sevoflurane receiving patients. Propofol group also showed higher protein level of connexin 43 (Cx43) than sevoflurane group. Besides, immunogold analysis showed its mitochondrial localization. The mRNA level of mtDNA and uncoupling protein (UCP2) were higher in propofol than sevoflurane patients, as well. On the other hand, there were no significant differences between groups in hemodynamic assessment, intensive care unit length of stay, troponin I and BNP level. Conclusions: Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms. It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase, while the effects of propofol occur through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2. Copyright (C) 2012 S. Karger AG, Basel
T2  - Cellular Physiology and Biochemistry
T1  - Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass
IS  - 1-2
VL  - 29
SP  - 973
EP  - 142
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1138
ER  - 

@article{
author = "Jović, Miomir Đ and Stančić, Ana and Nenadić, Dragan and Cekić, Olivera and Nezić, Dusko G and Milojević, Predrag S and Micović, Slobodan V and Buzadžić, Biljana J. and Korac, Aleksandra B and Otašević, Vesna and Janković, Aleksandra and Vučetić, Milica and Velicković, Ksenija D and Golić, Igor and Korać, Bato",
year = "2012",
abstract = "Background/Aims: Study elucidates and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis. Methods: Twenty-two patients were prospectively randomized in two groups regarding the anesthetic regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac injury and brain natriuretic peptide (BNP) were measured preoperatively and postoperatively. In tissue samples, taken from the interventricular septum, key mitochondrial molecules were determined by Western blot, real time PCR, as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis. Results: The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content was higher in propofol than sevoflurane receiving patients. Propofol group also showed higher protein level of connexin 43 (Cx43) than sevoflurane group. Besides, immunogold analysis showed its mitochondrial localization. The mRNA level of mtDNA and uncoupling protein (UCP2) were higher in propofol than sevoflurane patients, as well. On the other hand, there were no significant differences between groups in hemodynamic assessment, intensive care unit length of stay, troponin I and BNP level. Conclusions: Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms. It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase, while the effects of propofol occur through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2. Copyright (C) 2012 S. Karger AG, Basel",
journal = "Cellular Physiology and Biochemistry",
title = "Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass",
number = "1-2",
volume = "29",
pages = "973-142",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1138"
}

Jović, M. Đ., Stančić, A., Nenadić, D., Cekić, O., Nezić, D. G., Milojević, P. S., Micović, S. V., Buzadžić, B. J., Korac, A. B., Otašević, V., Janković, A., Vučetić, M., Velicković, K. D., Golić, I.,& Korać, B.. (2012). Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass. in Cellular Physiology and Biochemistry, 29(1-2), 973-142.
https://hdl.handle.net/21.15107/rcub_ibiss_1138

Jović MĐ, Stančić A, Nenadić D, Cekić O, Nezić DG, Milojević PS, Micović SV, Buzadžić BJ, Korac AB, Otašević V, Janković A, Vučetić M, Velicković KD, Golić I, Korać B. Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass. in Cellular Physiology and Biochemistry. 2012;29(1-2):973-142.
https://hdl.handle.net/21.15107/rcub_ibiss_1138 .

Jović, Miomir Đ, Stančić, Ana, Nenadić, Dragan, Cekić, Olivera, Nezić, Dusko G, Milojević, Predrag S, Micović, Slobodan V, Buzadžić, Biljana J., Korac, Aleksandra B, Otašević, Vesna, Janković, Aleksandra, Vučetić, Milica, Velicković, Ksenija D, Golić, Igor, Korać, Bato, "Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass" in Cellular Physiology and Biochemistry, 29, no. 1-2 (2012):973-142,
https://hdl.handle.net/21.15107/rcub_ibiss_1138 .

TY  - CONF
AU  - Vučetić, Milica
AU  - Stančić, Ana
AU  - Filipović, Milos R
AU  - Ivanović-Burmazović, Ivana S
AU  - Otašević, Vesna
AU  - Korac, Aleksandra B
AU  - Janković, Aleksandra
AU  - Buzadžić, Biljana J.
AU  - Velicković, Ksenija D
AU  - Markelić, Milica B
AU  - Golić, Igor
AU  - Korać, Bato
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1137
C3  - European Journal of Clinical Investigation
T1  - The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats
IS  - null
VL  - 42
SP  - 969
EP  - 76
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1137
ER  - 

@conference{
author = "Vučetić, Milica and Stančić, Ana and Filipović, Milos R and Ivanović-Burmazović, Ivana S and Otašević, Vesna and Korac, Aleksandra B and Janković, Aleksandra and Buzadžić, Biljana J. and Velicković, Ksenija D and Markelić, Milica B and Golić, Igor and Korać, Bato",
year = "2012",
journal = "European Journal of Clinical Investigation",
title = "The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats",
number = "null",
volume = "42",
pages = "969-76",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1137"
}

Vučetić, M., Stančić, A., Filipović, M. R., Ivanović-Burmazović, I. S., Otašević, V., Korac, A. B., Janković, A., Buzadžić, B. J., Velicković, K. D., Markelić, M. B., Golić, I.,& Korać, B.. (2012). The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats. in European Journal of Clinical Investigation, 42(null), 969-76.
https://hdl.handle.net/21.15107/rcub_ibiss_1137

Vučetić M, Stančić A, Filipović MR, Ivanović-Burmazović IS, Otašević V, Korac AB, Janković A, Buzadžić BJ, Velicković KD, Markelić MB, Golić I, Korać B. The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats. in European Journal of Clinical Investigation. 2012;42(null):969-76.
https://hdl.handle.net/21.15107/rcub_ibiss_1137 .

Vučetić, Milica, Stančić, Ana, Filipović, Milos R, Ivanović-Burmazović, Ivana S, Otašević, Vesna, Korac, Aleksandra B, Janković, Aleksandra, Buzadžić, Biljana J., Velicković, Ksenija D, Markelić, Milica B, Golić, Igor, Korać, Bato, "The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats" in European Journal of Clinical Investigation, 42, no. null (2012):969-76,
https://hdl.handle.net/21.15107/rcub_ibiss_1137 .

TY  - JOUR
AU  - Stančić, Ana
AU  - Rasić-Milutinović, Zorica R
AU  - Perunicić-Peković, Gordana B
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra B
AU  - Otašević, Vesna
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Korać, Bato
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1189
AB  - Diabetes and renal insufficiency are interrelated metabolic disorders closely associated with redox homeostasis disturbances. The aim of this study was to compare the activity of copper zinc,superoxide dismutase (CuZnSOD) in the erythrocytes of hypertensive diabetic patients with or without renal insufficiency with normal healthy control subjects. In both groups of diabetic patients, blood glucose level and the content of glycosylated hemoglobin (HbA(lc)) were higher than in the control group. However, CuZnSOD activity was significantly higher than control only in hypertensive diabetic patients with renal insufficiency. Our results suggest that disturbances in superoxide homeostasis do correlate with long-term complication in diabetes, i.e. diabetic renal insufficiency and hypertension.
T2  - Indian Journal of Biochemistry & Biophysics
T1  - Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients
IS  - 2
VL  - 49
EP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1189
ER  - 

@article{
author = "Stančić, Ana and Rasić-Milutinović, Zorica R and Perunicić-Peković, Gordana B and Buzadžić, Biljana J. and Korac, Aleksandra B and Otašević, Vesna and Janković, Aleksandra and Vučetić, Milica and Korać, Bato",
year = "2012",
abstract = "Diabetes and renal insufficiency are interrelated metabolic disorders closely associated with redox homeostasis disturbances. The aim of this study was to compare the activity of copper zinc,superoxide dismutase (CuZnSOD) in the erythrocytes of hypertensive diabetic patients with or without renal insufficiency with normal healthy control subjects. In both groups of diabetic patients, blood glucose level and the content of glycosylated hemoglobin (HbA(lc)) were higher than in the control group. However, CuZnSOD activity was significantly higher than control only in hypertensive diabetic patients with renal insufficiency. Our results suggest that disturbances in superoxide homeostasis do correlate with long-term complication in diabetes, i.e. diabetic renal insufficiency and hypertension.",
journal = "Indian Journal of Biochemistry & Biophysics",
title = "Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients",
number = "2",
volume = "49",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1189"
}

Stančić, A., Rasić-Milutinović, Z. R., Perunicić-Peković, G. B., Buzadžić, B. J., Korac, A. B., Otašević, V., Janković, A., Vučetić, M.,& Korać, B.. (2012). Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients. in Indian Journal of Biochemistry & Biophysics, 49(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1189

Stančić A, Rasić-Milutinović ZR, Perunicić-Peković GB, Buzadžić BJ, Korac AB, Otašević V, Janković A, Vučetić M, Korać B. Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients. in Indian Journal of Biochemistry & Biophysics. 2012;49(2):null-100.
https://hdl.handle.net/21.15107/rcub_ibiss_1189 .

Stančić, Ana, Rasić-Milutinović, Zorica R, Perunicić-Peković, Gordana B, Buzadžić, Biljana J., Korac, Aleksandra B, Otašević, Vesna, Janković, Aleksandra, Vučetić, Milica, Korać, Bato, "Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients" in Indian Journal of Biochemistry & Biophysics, 49, no. 2 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1189 .

TY  - CONF
AU  - Macanović, Biljana
AU  - Otašević, Vesna
AU  - Korac, Aleksandra B
AU  - Vučetić, Milica
AU  - Garalejić, Eliana
AU  - Ivanović-Burmazović, Ivana S
AU  - Filipović, Milos R
AU  - Buzadžić, Biljana J.
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Markelić, Milica B
AU  - Korać, Bato
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1212
C3  - Human Reproduction
T1  - Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO
IS  - null
VL  - 27
EP  - na
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1212
ER  - 

@conference{
author = "Macanović, Biljana and Otašević, Vesna and Korac, Aleksandra B and Vučetić, Milica and Garalejić, Eliana and Ivanović-Burmazović, Ivana S and Filipović, Milos R and Buzadžić, Biljana J. and Stančić, Ana and Janković, Aleksandra and Velicković, Ksenija D and Golić, Igor and Markelić, Milica B and Korać, Bato",
year = "2012",
journal = "Human Reproduction",
title = "Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO",
number = "null",
volume = "27",
pages = "na",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1212"
}

Macanović, B., Otašević, V., Korac, A. B., Vučetić, M., Garalejić, E., Ivanović-Burmazović, I. S., Filipović, M. R., Buzadžić, B. J., Stančić, A., Janković, A., Velicković, K. D., Golić, I., Markelić, M. B.,& Korać, B.. (2012). Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO. in Human Reproduction, 27(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1212

Macanović B, Otašević V, Korac AB, Vučetić M, Garalejić E, Ivanović-Burmazović IS, Filipović MR, Buzadžić BJ, Stančić A, Janković A, Velicković KD, Golić I, Markelić MB, Korać B. Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO. in Human Reproduction. 2012;27(null):null-na.
https://hdl.handle.net/21.15107/rcub_ibiss_1212 .

Macanović, Biljana, Otašević, Vesna, Korac, Aleksandra B, Vučetić, Milica, Garalejić, Eliana, Ivanović-Burmazović, Ivana S, Filipović, Milos R, Buzadžić, Biljana J., Stančić, Ana, Janković, Aleksandra, Velicković, Ksenija D, Golić, Igor, Markelić, Milica B, Korać, Bato, "Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO" in Human Reproduction, 27, no. null (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1212 .

TY  - JOUR
AU  - Buzadžić, Biljana J.
AU  - Vučetić, Milica
AU  - Janković, Aleksandra
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Korać, Bato
PY  - 2011
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/455
AB  - Oxidants, antioxidants and free radicals are terms that are associated with daily supplementation of antioxidants in the prevention of a wide range of diseases and pathology. Unfortunately, that kind of thinking, followed by insufficient knowledge of the redox mechanism, popularistically categorizes oxidants and antioxidants as bad and good. This paper is an attempt to examine their role in biological systems with a central place of redox regulation as a life compromise between these two extremes, based on previous knowledge. A try to get a perspective of the protective role of antioxidant and oxidant toxicity, and to perceive a reality in which their activity and/ or concentration in cells determines their role from pathology to the regulation of physiological processes. A special place in that reality is dedicated to gasotransmitters: nitric monoxide (NO), carbon monox­ide (CO) and hydrogen sulfide (H2S). .
AB  - Oksidanti, antioksidanti i slobodni radikali su termini koji se svakodnevno povezuju sa suplementacijom antioksidanata u prevenciji širokog spektra oboljenja i patologija. Nažalost, takav način razmišljanja, praćen nedovoljnim poznavanjem redoks mehanizama, popularistički kategorizuje oksidante i antioksidante na dobre i loše. Ovaj rad je pokušaj da se na bazi dosadašnjih saznanja sagleda njihova uloga u biološkim sistemima sa centralnim mestom redoks regulacije kao životnog kompromisa između ove dve krajnosti. Pokušaj da se između zaštitne uloge antioksidanata i toksičnosti oksidanata sagleda realnost u kojoj njihova aktivnost i/ili koncentracija u ćelijama determiniše njihovu ulogu od patologije do regulacije fizioloških procesa. Posebno mesto u toj realnosti posvećeno je gasotransmiterima: azot monoksidu (NO), ugljen monoksidu (CO) i vodonik sulfidu (H2S). .
T2  - Hrana i ishrana
T1  - Od Fentonove reakcije do savremenog koncepta redoks regulacije
T1  - From Fenton's reaction to modern concept of redox regulation
IS  - 1
VL  - 52
SP  - 1
EP  - 10
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_455
ER  - 

@article{
author = "Buzadžić, Biljana J. and Vučetić, Milica and Janković, Aleksandra and Stančić, Ana and Otašević, Vesna and Korać, Bato",
year = "2011, 2011",
abstract = "Oxidants, antioxidants and free radicals are terms that are associated with daily supplementation of antioxidants in the prevention of a wide range of diseases and pathology. Unfortunately, that kind of thinking, followed by insufficient knowledge of the redox mechanism, popularistically categorizes oxidants and antioxidants as bad and good. This paper is an attempt to examine their role in biological systems with a central place of redox regulation as a life compromise between these two extremes, based on previous knowledge. A try to get a perspective of the protective role of antioxidant and oxidant toxicity, and to perceive a reality in which their activity and/ or concentration in cells determines their role from pathology to the regulation of physiological processes. A special place in that reality is dedicated to gasotransmitters: nitric monoxide (NO), carbon monox­ide (CO) and hydrogen sulfide (H2S). ., Oksidanti, antioksidanti i slobodni radikali su termini koji se svakodnevno povezuju sa suplementacijom antioksidanata u prevenciji širokog spektra oboljenja i patologija. Nažalost, takav način razmišljanja, praćen nedovoljnim poznavanjem redoks mehanizama, popularistički kategorizuje oksidante i antioksidante na dobre i loše. Ovaj rad je pokušaj da se na bazi dosadašnjih saznanja sagleda njihova uloga u biološkim sistemima sa centralnim mestom redoks regulacije kao životnog kompromisa između ove dve krajnosti. Pokušaj da se između zaštitne uloge antioksidanata i toksičnosti oksidanata sagleda realnost u kojoj njihova aktivnost i/ili koncentracija u ćelijama determiniše njihovu ulogu od patologije do regulacije fizioloških procesa. Posebno mesto u toj realnosti posvećeno je gasotransmiterima: azot monoksidu (NO), ugljen monoksidu (CO) i vodonik sulfidu (H2S). .",
journal = "Hrana i ishrana",
title = "Od Fentonove reakcije do savremenog koncepta redoks regulacije, From Fenton's reaction to modern concept of redox regulation",
number = "1",
volume = "52",
pages = "1-10",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_455"
}

Buzadžić, B. J., Vučetić, M., Janković, A., Stančić, A., Otašević, V.,& Korać, B.. (2011). Od Fentonove reakcije do savremenog koncepta redoks regulacije. in Hrana i ishrana, 52(1), 1-10.
https://hdl.handle.net/21.15107/rcub_ibiss_455

Buzadžić BJ, Vučetić M, Janković A, Stančić A, Otašević V, Korać B. Od Fentonove reakcije do savremenog koncepta redoks regulacije. in Hrana i ishrana. 2011;52(1):1-10.
https://hdl.handle.net/21.15107/rcub_ibiss_455 .

Buzadžić, Biljana J., Vučetić, Milica, Janković, Aleksandra, Stančić, Ana, Otašević, Vesna, Korać, Bato, "Od Fentonove reakcije do savremenog koncepta redoks regulacije" in Hrana i ishrana, 52, no. 1 (2011):1-10,
https://hdl.handle.net/21.15107/rcub_ibiss_455 .

TY  - JOUR
AU  - Vučetić, Milica
AU  - Otašević, Vesna
AU  - Korac, Aleksandra B
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Markelić, Milica B
AU  - Golić, Igor
AU  - Velicković, Ksenija D
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1243
AB  - Background: Brown adipose tissue thermogenic program includes complex molecular and structural changes. However, energetic aspects of this process are poorly depicted. Methods: We investigated time-dependent reprogramming of interscapular brown adipose tissue (IBAT) energy metabolism during cold-acclimation, as well as the effects of nitric oxide ((center dot)NO) on those changes. Rats were exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21. and 45 days, and divided into three groups: control, treated with L-arginine, and treated with N(omega)-nitro-L-arginine methyl ester (L-NAME). Results: In the early phase of cold-acclimation (up to 7 days), the protein levels of all metabolic parameters and oxidative phosphorylation components were below the control. However, metabolic parameters and respiratory chain components entered a new homeostatic level in the late phase of cold-acclimation. These changes were accompanied with increased protein levels of phospho-AMP-dependent protein kinase-alpha (phospho-AMPK alpha) on the first day of cold-acclimation, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) throughout early cold-acclimation. L-arginine positively affected protein expression of enzymes involved in glucose metabolism and beta-oxidation of fatty acids in the early phase of cold-acclimation, and oxidative phosphorylation components throughout cold-acclimation. In contrast, L-NAME had the opposite effects. Conclusion: Results suggest that IBAT structural remodeling is followed by energy metabolism reprogramming, which control might be orchestrated by the action of AMPK alpha and HIF-1 alpha. Data also indicated the involvement of L-arginine-(center dot)NO in the regulation of IBAT metabolism. General significance: Results obtained in this study might be of great importance for elucidating regulatory pathways governing energy metabolism in both physiological and pathophysiological states. (C) 2011 Elsevier B.V. All rights reserved.
T2  - Biochimica et Biophysica Acta-General Subjects
T1  - Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha
IS  - 12
VL  - 1810
EP  - 1261
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1243
ER  - 

@article{
author = "Vučetić, Milica and Otašević, Vesna and Korac, Aleksandra B and Stančić, Ana and Janković, Aleksandra and Markelić, Milica B and Golić, Igor and Velicković, Ksenija D and Buzadžić, Biljana J. and Korać, Bato",
year = "2011",
abstract = "Background: Brown adipose tissue thermogenic program includes complex molecular and structural changes. However, energetic aspects of this process are poorly depicted. Methods: We investigated time-dependent reprogramming of interscapular brown adipose tissue (IBAT) energy metabolism during cold-acclimation, as well as the effects of nitric oxide ((center dot)NO) on those changes. Rats were exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21. and 45 days, and divided into three groups: control, treated with L-arginine, and treated with N(omega)-nitro-L-arginine methyl ester (L-NAME). Results: In the early phase of cold-acclimation (up to 7 days), the protein levels of all metabolic parameters and oxidative phosphorylation components were below the control. However, metabolic parameters and respiratory chain components entered a new homeostatic level in the late phase of cold-acclimation. These changes were accompanied with increased protein levels of phospho-AMP-dependent protein kinase-alpha (phospho-AMPK alpha) on the first day of cold-acclimation, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) throughout early cold-acclimation. L-arginine positively affected protein expression of enzymes involved in glucose metabolism and beta-oxidation of fatty acids in the early phase of cold-acclimation, and oxidative phosphorylation components throughout cold-acclimation. In contrast, L-NAME had the opposite effects. Conclusion: Results suggest that IBAT structural remodeling is followed by energy metabolism reprogramming, which control might be orchestrated by the action of AMPK alpha and HIF-1 alpha. Data also indicated the involvement of L-arginine-(center dot)NO in the regulation of IBAT metabolism. General significance: Results obtained in this study might be of great importance for elucidating regulatory pathways governing energy metabolism in both physiological and pathophysiological states. (C) 2011 Elsevier B.V. All rights reserved.",
journal = "Biochimica et Biophysica Acta-General Subjects",
title = "Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha",
number = "12",
volume = "1810",
pages = "1261",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1243"
}

Vučetić, M., Otašević, V., Korac, A. B., Stančić, A., Janković, A., Markelić, M. B., Golić, I., Velicković, K. D., Buzadžić, B. J.,& Korać, B.. (2011). Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha. in Biochimica et Biophysica Acta-General Subjects, 1810(12).
https://hdl.handle.net/21.15107/rcub_ibiss_1243

Vučetić M, Otašević V, Korac AB, Stančić A, Janković A, Markelić MB, Golić I, Velicković KD, Buzadžić BJ, Korać B. Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha. in Biochimica et Biophysica Acta-General Subjects. 2011;1810(12):null-1261.
https://hdl.handle.net/21.15107/rcub_ibiss_1243 .

Vučetić, Milica, Otašević, Vesna, Korac, Aleksandra B, Stančić, Ana, Janković, Aleksandra, Markelić, Milica B, Golić, Igor, Velicković, Ksenija D, Buzadžić, Biljana J., Korać, Bato, "Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha" in Biochimica et Biophysica Acta-General Subjects, 1810, no. 12 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1243 .

TY  - JOUR
AU  - Otašević, Vesna
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra B
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Korać, Bato
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1281
AB  - Study elucidates molecular mechanisms underlying activation of catalase and glutathione peroxidase (GSH-Px) during cold-exposure by examining time-dependent changes in their mRNA, protein expression and activity, in interscapular brown adipose tissue (IBAT) of rats kept at room temperature (22 +/- 1 degrees C), or subjected to cold (4 +/- 1 degrees C) for 1, 3, 7, 12, 21 and 45 days. To examine involvement of nitric oxide (*NO) in catalase and GSH-Px regulation, rats were treated with L-arginine or N((1))-nitro-L-arginine-methyl ester (L-NAME). In all groups, cold increased catalase mRNA, protein expression and activity from day 3 to day 45 of acclimation. However, cold-acclimation increased GSH-Px mRNA content on day 3, protein content from day 1 to day 45 and activity no sooner than on day 45. At room temperature, 21- and 45-day L-arginine and L-NAME supplementation increased catalase and GSH-Px mRNA expression, but decreased their activity. Concomitantly, catalase protein content decreased, while GSH-Px protein expression increased compared to control. Data show that cold is dominant stimulus that determines IBAT catalase and GSH-Px responses, by setting tissue metabolic state. In thermogenic-active tissue, catalase is regulated on transcriptional level, while GSH-Px is regulated post-translationally. On the other side, it was shown that *NO affects catalase and GSH-Px only in thermogenic-inactive tissue. (C) 2011 Elsevier Ltd. All rights reserved.
T2  - Journal of Thermal Biology
T1  - Effects of L-arginine and L-NAME supplementation on mRNA, protein expression and activity of catalase and glutathione peroxidase in brown adipose tissue of rats acclimated to different temperatures
IS  - 5
VL  - 36
EP  - 276
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1281
ER  - 

@article{
author = "Otašević, Vesna and Buzadžić, Biljana J. and Korac, Aleksandra B and Stančić, Ana and Janković, Aleksandra and Vučetić, Milica and Korać, Bato",
year = "2011",
abstract = "Study elucidates molecular mechanisms underlying activation of catalase and glutathione peroxidase (GSH-Px) during cold-exposure by examining time-dependent changes in their mRNA, protein expression and activity, in interscapular brown adipose tissue (IBAT) of rats kept at room temperature (22 +/- 1 degrees C), or subjected to cold (4 +/- 1 degrees C) for 1, 3, 7, 12, 21 and 45 days. To examine involvement of nitric oxide (*NO) in catalase and GSH-Px regulation, rats were treated with L-arginine or N((1))-nitro-L-arginine-methyl ester (L-NAME). In all groups, cold increased catalase mRNA, protein expression and activity from day 3 to day 45 of acclimation. However, cold-acclimation increased GSH-Px mRNA content on day 3, protein content from day 1 to day 45 and activity no sooner than on day 45. At room temperature, 21- and 45-day L-arginine and L-NAME supplementation increased catalase and GSH-Px mRNA expression, but decreased their activity. Concomitantly, catalase protein content decreased, while GSH-Px protein expression increased compared to control. Data show that cold is dominant stimulus that determines IBAT catalase and GSH-Px responses, by setting tissue metabolic state. In thermogenic-active tissue, catalase is regulated on transcriptional level, while GSH-Px is regulated post-translationally. On the other side, it was shown that *NO affects catalase and GSH-Px only in thermogenic-inactive tissue. (C) 2011 Elsevier Ltd. All rights reserved.",
journal = "Journal of Thermal Biology",
title = "Effects of L-arginine and L-NAME supplementation on mRNA, protein expression and activity of catalase and glutathione peroxidase in brown adipose tissue of rats acclimated to different temperatures",
number = "5",
volume = "36",
pages = "276",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1281"
}

Otašević, V., Buzadžić, B. J., Korac, A. B., Stančić, A., Janković, A., Vučetić, M.,& Korać, B.. (2011). Effects of L-arginine and L-NAME supplementation on mRNA, protein expression and activity of catalase and glutathione peroxidase in brown adipose tissue of rats acclimated to different temperatures. in Journal of Thermal Biology, 36(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1281

Otašević V, Buzadžić BJ, Korac AB, Stančić A, Janković A, Vučetić M, Korać B. Effects of L-arginine and L-NAME supplementation on mRNA, protein expression and activity of catalase and glutathione peroxidase in brown adipose tissue of rats acclimated to different temperatures. in Journal of Thermal Biology. 2011;36(5):null-276.
https://hdl.handle.net/21.15107/rcub_ibiss_1281 .

Otašević, Vesna, Buzadžić, Biljana J., Korac, Aleksandra B, Stančić, Ana, Janković, Aleksandra, Vučetić, Milica, Korać, Bato, "Effects of L-arginine and L-NAME supplementation on mRNA, protein expression and activity of catalase and glutathione peroxidase in brown adipose tissue of rats acclimated to different temperatures" in Journal of Thermal Biology, 36, no. 5 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1281 .

TY  - JOUR
AU  - Markelić, Milica B
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Buzadžić, Biljana J.
AU  - Korać, Bato
AU  - Korac, Aleksandra B
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1324
AB  - The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsulinaemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonely) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-alpha) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone.
T2  - European Journal of Histochemistry
T1  - Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-alpha
IS  - 4
VL  - 55
EP  - 193
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1324
ER  - 

@article{
author = "Markelić, Milica B and Velicković, Ksenija D and Golić, Igor and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Vučetić, Milica and Buzadžić, Biljana J. and Korać, Bato and Korac, Aleksandra B",
year = "2011",
abstract = "The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsulinaemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonely) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-alpha) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone.",
journal = "European Journal of Histochemistry",
title = "Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-alpha",
number = "4",
volume = "55",
pages = "193",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1324"
}

Markelić, M. B., Velicković, K. D., Golić, I., Otašević, V., Stančić, A., Janković, A., Vučetić, M., Buzadžić, B. J., Korać, B.,& Korac, A. B.. (2011). Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-alpha. in European Journal of Histochemistry, 55(4).
https://hdl.handle.net/21.15107/rcub_ibiss_1324

Markelić MB, Velicković KD, Golić I, Otašević V, Stančić A, Janković A, Vučetić M, Buzadžić BJ, Korać B, Korac AB. Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-alpha. in European Journal of Histochemistry. 2011;55(4):null-193.
https://hdl.handle.net/21.15107/rcub_ibiss_1324 .

Markelić, Milica B, Velicković, Ksenija D, Golić, Igor, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Vučetić, Milica, Buzadžić, Biljana J., Korać, Bato, Korac, Aleksandra B, "Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-alpha" in European Journal of Histochemistry, 55, no. 4 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1324 .

TY  - CONF
AU  - Markelić, Milica B
AU  - Velicković, Ksenija D
AU  - Golić, Igor
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Janković, Aleksandra
AU  - Vučetić, Milica
AU  - Korać, Bato
AU  - Buzadžić, Biljana J.
AU  - Korac, Aleksandra B
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1314
C3  - Journal of Vascular Research
T1  - Insulin-induced microcirculation Remodelling in the rat brown adipose tissue
IS  - null
VL  - 48
EP  - 135
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1314
ER  - 

@conference{
author = "Markelić, Milica B and Velicković, Ksenija D and Golić, Igor and Otašević, Vesna and Stančić, Ana and Janković, Aleksandra and Vučetić, Milica and Korać, Bato and Buzadžić, Biljana J. and Korac, Aleksandra B",
year = "2011",
journal = "Journal of Vascular Research",
title = "Insulin-induced microcirculation Remodelling in the rat brown adipose tissue",
number = "null",
volume = "48",
pages = "135",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1314"
}

Markelić, M. B., Velicković, K. D., Golić, I., Otašević, V., Stančić, A., Janković, A., Vučetić, M., Korać, B., Buzadžić, B. J.,& Korac, A. B.. (2011). Insulin-induced microcirculation Remodelling in the rat brown adipose tissue. in Journal of Vascular Research, 48(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1314

Markelić MB, Velicković KD, Golić I, Otašević V, Stančić A, Janković A, Vučetić M, Korać B, Buzadžić BJ, Korac AB. Insulin-induced microcirculation Remodelling in the rat brown adipose tissue. in Journal of Vascular Research. 2011;48(null):null-135.
https://hdl.handle.net/21.15107/rcub_ibiss_1314 .

Markelić, Milica B, Velicković, Ksenija D, Golić, Igor, Otašević, Vesna, Stančić, Ana, Janković, Aleksandra, Vučetić, Milica, Korać, Bato, Buzadžić, Biljana J., Korac, Aleksandra B, "Insulin-induced microcirculation Remodelling in the rat brown adipose tissue" in Journal of Vascular Research, 48, no. null (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1314 .