TY  - JOUR
AU  - Adžić, Miroslav
AU  - Lukić, Iva
AU  - Mitić, Milos Z
AU  - Đorđević, Jelena D
AU  - Elaković, Ivana
AU  - Đorđević, Ana
AU  - Krstić-Demonacos, Marija
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/940
AB  - Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fiuoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fiuoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. (C) 2013 Elsevier Ltd. All rights reserved.
T2  - Psychoneuroendocrinology
T1  - Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism
IS  - 12
VL  - 38
SP  - 1459
EP  - 2924
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_940
ER  - 

@article{
author = "Adžić, Miroslav and Lukić, Iva and Mitić, Milos Z and Đorđević, Jelena D and Elaković, Ivana and Đorđević, Ana and Krstić-Demonacos, Marija and Matić, Gordana and Radojcić, Marija B",
year = "2013",
abstract = "Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fiuoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fiuoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. (C) 2013 Elsevier Ltd. All rights reserved.",
journal = "Psychoneuroendocrinology",
title = "Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism",
number = "12",
volume = "38",
pages = "1459-2924",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_940"
}

Adžić, M., Lukić, I., Mitić, M. Z., Đorđević, J. D., Elaković, I., Đorđević, A., Krstić-Demonacos, M., Matić, G.,& Radojcić, M. B.. (2013). Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. in Psychoneuroendocrinology, 38(12), 1459-2924.
https://hdl.handle.net/21.15107/rcub_ibiss_940

Adžić M, Lukić I, Mitić MZ, Đorđević JD, Elaković I, Đorđević A, Krstić-Demonacos M, Matić G, Radojcić MB. Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. in Psychoneuroendocrinology. 2013;38(12):1459-2924.
https://hdl.handle.net/21.15107/rcub_ibiss_940 .

Adžić, Miroslav, Lukić, Iva, Mitić, Milos Z, Đorđević, Jelena D, Elaković, Ivana, Đorđević, Ana, Krstić-Demonacos, Marija, Matić, Gordana, Radojcić, Marija B, "Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism" in Psychoneuroendocrinology, 38, no. 12 (2013):1459-2924,
https://hdl.handle.net/21.15107/rcub_ibiss_940 .

TY  - JOUR
AU  - Popović, Natasa M
AU  - Ruždijić, Sabera
AU  - Kanazir, Dusan T.
AU  - Niciforović, Ana
AU  - Adžić, Miroslav
AU  - Paraskevopoulou, Elissavet
AU  - Pantelidou, Constantia
AU  - Radojcić, Marija B
AU  - Demonacos, Constantinos
AU  - Krstić-Demonacos, Marija
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1375
AB  - The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.
T2  - Steroids
T1  - Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae
IS  - 6
VL  - 75
EP  - 465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1375
ER  - 

@article{
author = "Popović, Natasa M and Ruždijić, Sabera and Kanazir, Dusan T. and Niciforović, Ana and Adžić, Miroslav and Paraskevopoulou, Elissavet and Pantelidou, Constantia and Radojcić, Marija B and Demonacos, Constantinos and Krstić-Demonacos, Marija",
year = "2010",
abstract = "The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.",
journal = "Steroids",
title = "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae",
number = "6",
volume = "75",
pages = "465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1375"
}

Popović, N. M., Ruždijić, S., Kanazir, D. T., Niciforović, A., Adžić, M., Paraskevopoulou, E., Pantelidou, C., Radojcić, M. B., Demonacos, C.,& Krstić-Demonacos, M.. (2010). Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids, 75(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1375

Popović NM, Ruždijić S, Kanazir DT, Niciforović A, Adžić M, Paraskevopoulou E, Pantelidou C, Radojcić MB, Demonacos C, Krstić-Demonacos M. Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids. 2010;75(6):null-465.
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

Popović, Natasa M, Ruždijić, Sabera, Kanazir, Dusan T., Niciforović, Ana, Adžić, Miroslav, Paraskevopoulou, Elissavet, Pantelidou, Constantia, Radojcić, Marija B, Demonacos, Constantinos, Krstić-Demonacos, Marija, "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae" in Steroids, 75, no. 6 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

TY  - JOUR
AU  - Đorđević-Marković, R
AU  - Radić, O
AU  - Jelić, V
AU  - Radojcić, M
AU  - Rapić-Otrin, V
AU  - Ruždijić, Sabera
AU  - Krstić-Demonacos, Marija
AU  - Kanazir, Selma
AU  - Kanazir, Dusan T.
PY  - 1999
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1840
AB  - The role of the glucocorticoid receptor (GR) in senescence was studied in rats of increasing age. Statistically significant changes in the number of GRs from rat liver were detected, whereas the affinity for the ligand triamcinolone acetonide (TA) did not change with increasing age, and was in the range of 1-2 nM. In all cases the number of receptors was lower in rats treated with hormone in vivo relative to untreated animals. In addition, we have found changes in GR activation, as measured by the binding to DNA cellulose in the mentioned age groups. Furthermore, expression of the glucocorticoid hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showed age-related alterations. We conclude that receptor function shows oscillatory changes during ageing. In addition, response to GH generally declines towards the older age. This. specific periodicity in functional characteristics of the GR may reconcile conflicting results about the receptor number and properties during the ageing process, and marks particular age at which individual organism shows the highest or the lowest sensitivity to the actions of GH. (C) 1999 Elsevier Science Inc. All rights reserved.
T2  - Experimental Gerontology
T1  - Glucocorticoid receptors in ageing rats
IS  - 8
VL  - 34
EP  - 982
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1840
ER  - 

@article{
author = "Đorđević-Marković, R and Radić, O and Jelić, V and Radojcić, M and Rapić-Otrin, V and Ruždijić, Sabera and Krstić-Demonacos, Marija and Kanazir, Selma and Kanazir, Dusan T.",
year = "1999",
abstract = "The role of the glucocorticoid receptor (GR) in senescence was studied in rats of increasing age. Statistically significant changes in the number of GRs from rat liver were detected, whereas the affinity for the ligand triamcinolone acetonide (TA) did not change with increasing age, and was in the range of 1-2 nM. In all cases the number of receptors was lower in rats treated with hormone in vivo relative to untreated animals. In addition, we have found changes in GR activation, as measured by the binding to DNA cellulose in the mentioned age groups. Furthermore, expression of the glucocorticoid hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showed age-related alterations. We conclude that receptor function shows oscillatory changes during ageing. In addition, response to GH generally declines towards the older age. This. specific periodicity in functional characteristics of the GR may reconcile conflicting results about the receptor number and properties during the ageing process, and marks particular age at which individual organism shows the highest or the lowest sensitivity to the actions of GH. (C) 1999 Elsevier Science Inc. All rights reserved.",
journal = "Experimental Gerontology",
title = "Glucocorticoid receptors in ageing rats",
number = "8",
volume = "34",
pages = "982",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1840"
}

Đorđević-Marković, R., Radić, O., Jelić, V., Radojcić, M., Rapić-Otrin, V., Ruždijić, S., Krstić-Demonacos, M., Kanazir, S.,& Kanazir, D. T.. (1999). Glucocorticoid receptors in ageing rats. in Experimental Gerontology, 34(8).
https://hdl.handle.net/21.15107/rcub_ibiss_1840

Đorđević-Marković R, Radić O, Jelić V, Radojcić M, Rapić-Otrin V, Ruždijić S, Krstić-Demonacos M, Kanazir S, Kanazir DT. Glucocorticoid receptors in ageing rats. in Experimental Gerontology. 1999;34(8):null-982.
https://hdl.handle.net/21.15107/rcub_ibiss_1840 .

Đorđević-Marković, R, Radić, O, Jelić, V, Radojcić, M, Rapić-Otrin, V, Ruždijić, Sabera, Krstić-Demonacos, Marija, Kanazir, Selma, Kanazir, Dusan T., "Glucocorticoid receptors in ageing rats" in Experimental Gerontology, 34, no. 8 (1999),
https://hdl.handle.net/21.15107/rcub_ibiss_1840 .