Wellcome Trust [069024]

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Wellcome Trust [069024]

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Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain

Adžić, Miroslav; Đorđević, Jelena D.; Đorđević, Ana D.; Nićiforović, Ana; Demonacos, Constantinos; Radoičić, Marija B.; Krstić-Demonacos, Marija

(2009)

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Đorđević, Jelena D.
AU  - Đorđević, Ana D.
AU  - Nićiforović, Ana
AU  - Demonacos, Constantinos
AU  - Radoičić, Marija B.
AU  - Krstić-Demonacos, Marija
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3848
AB  - Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic-pituitary-adrenal (HPA) axis activity. We investigated the effects of chronic 2 1 day isolation of Wistar rats on the extrinsic negative feedback part of I-IPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine 232 and serine 246, expression of GR, regulated genes: GR, CRF and brain-derived neurotropic factor (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that phosphorylate GR. These parameters were also determined in animals subjected to acute 30 min immobilization, which was taken as normal adaptive response to stress. In isolated animals, we found decreased CORT, whereas, in animals exposed to acute immobilization, CORT was markedly increased. Even though the GR was predominantly localized in the nucleus of HIPPO and PFC in acute, but not in chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated under both acute and chronic stresses. Thus, the transcriptional activity of GR under chronic isolation did not seem to be exclusively dependent on high serum CORT levels nor on the subcellular location of the GR protein. Rather, it resulted front the increased Cdk5 activation and phosphorylation of the nuclear GR at serine 232 and the decreased JNK activity reflected in decreased phosphorylation of the nuclear GR at serine 246. Our study suggests that this nuclear isoform of hippocampal and cortical GR may be related to hypocorticism i.e. HPA axis hypoactivity under chronic isolation stress. journal of Endocrinology (2009) 202, 87-97
T2  - Journal of Endocrinology
T1  - Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain
VL  - 202
IS  - 1
SP  - 87
EP  - 97
DO  - 10.1677/JOE-08-0509
ER  - 
@article{
author = "Adžić, Miroslav and Đorđević, Jelena D. and Đorđević, Ana D. and Nićiforović, Ana and Demonacos, Constantinos and Radoičić, Marija B. and Krstić-Demonacos, Marija",
year = "2009",
abstract = "Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic-pituitary-adrenal (HPA) axis activity. We investigated the effects of chronic 2 1 day isolation of Wistar rats on the extrinsic negative feedback part of I-IPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine 232 and serine 246, expression of GR, regulated genes: GR, CRF and brain-derived neurotropic factor (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that phosphorylate GR. These parameters were also determined in animals subjected to acute 30 min immobilization, which was taken as normal adaptive response to stress. In isolated animals, we found decreased CORT, whereas, in animals exposed to acute immobilization, CORT was markedly increased. Even though the GR was predominantly localized in the nucleus of HIPPO and PFC in acute, but not in chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated under both acute and chronic stresses. Thus, the transcriptional activity of GR under chronic isolation did not seem to be exclusively dependent on high serum CORT levels nor on the subcellular location of the GR protein. Rather, it resulted front the increased Cdk5 activation and phosphorylation of the nuclear GR at serine 232 and the decreased JNK activity reflected in decreased phosphorylation of the nuclear GR at serine 246. Our study suggests that this nuclear isoform of hippocampal and cortical GR may be related to hypocorticism i.e. HPA axis hypoactivity under chronic isolation stress. journal of Endocrinology (2009) 202, 87-97",
journal = "Journal of Endocrinology",
title = "Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain",
volume = "202",
number = "1",
pages = "87-97",
doi = "10.1677/JOE-08-0509"
}
Adžić, M., Đorđević, J. D., Đorđević, A. D., Nićiforović, A., Demonacos, C., Radoičić, M. B.,& Krstić-Demonacos, M.. (2009). Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain. in Journal of Endocrinology, 202(1), 87-97.
https://doi.org/10.1677/JOE-08-0509
Adžić M, Đorđević JD, Đorđević AD, Nićiforović A, Demonacos C, Radoičić MB, Krstić-Demonacos M. Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain. in Journal of Endocrinology. 2009;202(1):87-97.
doi:10.1677/JOE-08-0509 .
Adžić, Miroslav, Đorđević, Jelena D., Đorđević, Ana D., Nićiforović, Ana, Demonacos, Constantinos, Radoičić, Marija B., Krstić-Demonacos, Marija, "Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain" in Journal of Endocrinology, 202, no. 1 (2009):87-97,
https://doi.org/10.1677/JOE-08-0509 . .
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The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats

Adžić, Miroslav; Đorđević, Ana D.; Demonacos, Constantinos; Krstić-Demonacos, Marija; Radojčić, Marija

(2009)

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Đorđević, Ana D.
AU  - Demonacos, Constantinos
AU  - Krstić-Demonacos, Marija
AU  - Radojčić, Marija
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3810
AB  - Mitochondrial dysfunction is increasingly recognized as a key component in compromised neuroendocrine stress response and. among other etiological causes. it may also involve action of glucocorticoid hormones. In the current study we followed glucocorticoid receptor and Identified its mitochondrial phosphoisophorms in hippocampus and prefrontal brain cortex of Wistar male rats subjected to acute. chronic and combined neuroendocrine stresses. In both brain structures chronic social isolation caused m,irked increase in mitochondrial glucocorticoid receptor that was preferentially phosphorylated at serine 232 compared to serine 246 or serine 171. This increase corresponded with the decreased expression of mitochondrially encoded cytochrome oxidase subunits 1 and 3 in hippocampus, and with their increased expression in prefrontal brain cortex. Prefrontal brain cortex appeared to be more sensitive to chronic stress, since it exibited higher levels of mitochondrial Bax and cytoplasmic Bcl2 compared to hippocampus. Chronic stress also altered the response of both brain structures to subsequent acute stress according to the studied parameters. Therefore, prolonged social isolation may cause susceptibility to mitochondria triggered proapototic signalling. which at least in part may be mediated by the glucocorticoid receptor dependent mechanism. (C) 2009 Elsevier Ltd All rights reserved.
T2  - International Journal of Biochemistry and Cell Biology
T1  - The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats
VL  - 41
IS  - 11
SP  - 2181
EP  - 2188
DO  - 10.1016/j.biocel.2009.04.001
ER  - 
@article{
author = "Adžić, Miroslav and Đorđević, Ana D. and Demonacos, Constantinos and Krstić-Demonacos, Marija and Radojčić, Marija",
year = "2009",
abstract = "Mitochondrial dysfunction is increasingly recognized as a key component in compromised neuroendocrine stress response and. among other etiological causes. it may also involve action of glucocorticoid hormones. In the current study we followed glucocorticoid receptor and Identified its mitochondrial phosphoisophorms in hippocampus and prefrontal brain cortex of Wistar male rats subjected to acute. chronic and combined neuroendocrine stresses. In both brain structures chronic social isolation caused m,irked increase in mitochondrial glucocorticoid receptor that was preferentially phosphorylated at serine 232 compared to serine 246 or serine 171. This increase corresponded with the decreased expression of mitochondrially encoded cytochrome oxidase subunits 1 and 3 in hippocampus, and with their increased expression in prefrontal brain cortex. Prefrontal brain cortex appeared to be more sensitive to chronic stress, since it exibited higher levels of mitochondrial Bax and cytoplasmic Bcl2 compared to hippocampus. Chronic stress also altered the response of both brain structures to subsequent acute stress according to the studied parameters. Therefore, prolonged social isolation may cause susceptibility to mitochondria triggered proapototic signalling. which at least in part may be mediated by the glucocorticoid receptor dependent mechanism. (C) 2009 Elsevier Ltd All rights reserved.",
journal = "International Journal of Biochemistry and Cell Biology",
title = "The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats",
volume = "41",
number = "11",
pages = "2181-2188",
doi = "10.1016/j.biocel.2009.04.001"
}
Adžić, M., Đorđević, A. D., Demonacos, C., Krstić-Demonacos, M.,& Radojčić, M.. (2009). The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats. in International Journal of Biochemistry and Cell Biology, 41(11), 2181-2188.
https://doi.org/10.1016/j.biocel.2009.04.001
Adžić M, Đorđević AD, Demonacos C, Krstić-Demonacos M, Radojčić M. The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats. in International Journal of Biochemistry and Cell Biology. 2009;41(11):2181-2188.
doi:10.1016/j.biocel.2009.04.001 .
Adžić, Miroslav, Đorđević, Ana D., Demonacos, Constantinos, Krstić-Demonacos, Marija, Radojčić, Marija, "The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats" in International Journal of Biochemistry and Cell Biology, 41, no. 11 (2009):2181-2188,
https://doi.org/10.1016/j.biocel.2009.04.001 . .
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