Journal
BRAIN RESEARCH
Volume 1286, Issue -, Pages 1-12Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2009.06.036
Keywords
Immunophilins; FKBP52; FKBP51; Glucocorticoid receptor; FK506-binding proteins; Nuclear translocation
Categories
Funding
- United States National Institutes of Health [MH076681, R01MH079881, R41MH079728, R25MH074508, R25MH081482, P30 MH62512, R01 NS050621, T32 EB001026]
- Genomics Core at the UCSD Center for AIDS Research [AI36214]
- San Diego Veterans Medical Research Foundation
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Mood disorders associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis are common psychiatric conditions. The glucocorticoid receptor (GR) is a steroid-activated nuclear receptor that, upon binding to cortisol, translocates to the nucleus where it targets genes related to neuronal metabolism and plasticity. in patients suffering from major depressive disorder (MDD), hypercortisolemia is a common finding. In the current study we investigated the molecular events associated with the FK506 binding proteins (FKBP) -52 and -51 response to cortisol exposure in neuronal cell cultures and their effect on GR translocation. We noted that FK506 altered nuclear localization of the GR and inhibited expression of GR-responsive genes. Furthermore, siRNA knockdown of FKBP4 gene, coding for the immunophilin FKBP52, inhibited cortisol-activated GR nuclear translocation, while knockdown of FKBP5, coding for immunophilin FKBP51, was associated with increased baseline GR nuclear localization. We propose that immunophilins are modulators of the cortisol-HPA axis response to stress and related chronic brain disorders. (C) 2009 Elsevier B.V. All rights reserved.
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