Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients

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• 作者：Iva Lukic (1)
  Milos Mitic (1)
  Ivan Soldatovic (2)
  Milica Jovicic (3)
  Nadja Maric (2) (3)
  Jelena Radulovic (4)
  Miroslav Adzic (1)
  
  1. Laboratory of Molecular Biology and Endocrinology ; VINCA Institute of Nuclear Sciences ; University of Belgrade ; P.O. Box-522-MBE090 ; 11001 ; Belgrade ; Serbia
  2. Faculty of Medicine ; University of Belgrade ; Dr Subotica 8 ; 11000 ; Belgrade ; Serbia
  3. Clinic for Psychiatry ; Clinical Centre of Serbia ; Pasterova 2 ; 11000 ; Belgrade ; Serbia
  4. Department of Psychiatry and Behavioral Sciences ; The Asher Center for Study and Treatment of Depressive Disorders ; Feinberg School of Medicine ; Northwestern University ; Chicago ; IL ; 60611 ; USA
  
• 关键词：Major depressive disorder ; Glucocorticoid receptor ; FKBP5 ; GILZ
• 刊名：Journal of Molecular Neuroscience
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：55
• 期：4
• 页码：951-958
• 全文大小：365 KB
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• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166

文摘

We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.