title: Accumulation of cytoplasmic glucocorticoid receptor is related to elevation of FKBP5 in lymphocytes of depressed patients.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, P.O. Box-522-MBE090, 11001, Belgrade, Serbia, iwa@vinca.rs.
authors.forename: Iva
authors.initials: I
authors.lastname: Lukic
authors.forename: Milos
authors.initials: M
authors.lastname: Mitic
authors.forename: Ivan
authors.initials: I
authors.lastname: Soldatovic
authors.forename: Milica
authors.initials: M
authors.lastname: Jovicic
authors.forename: Nadja
authors.initials: N
authors.lastname: Maric
authors.forename: Jelena
authors.initials: J
authors.lastname: Radulovic
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099159:Tacrolimus Binding Protein 5; C404226:TSC22D3 protein, human