Document Detail


Region-specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain.
MedLine Citation:
PMID:  16895583     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The hippocampal glucocorticoid receptor (GR) is involved in negative feedback regulation of the hypothalamo-pituitary-adrenal axis and is believed to transduce the deleterious effects of glucocorticoids in depression and age-related memory loss. Regulation and intracellular trafficking of the GR are critical determinants of GR action in both health and disease. Here, we show dynamic regulation of GR and its interaction with its principal intracellular chaperone, heat-shock protein (HSP) 90, across the circadian cycle. Our initial experiments indicate that cytosolic hippocampal GR protein is elevated in the evening (PM), whereas nuclear GR and cytosolic HSP90, HSP70 and heat-shock cognate 70 (HSC70), are unchanged. In contrast, there are no changes in examined proteins in the hypothalamus. Immunoprecipitation experiments reveal increased GR-HSP90 associations in the hippocampus in the PM, whereas binding in the hypothalamus is decreased in the PM. Given that GR requires HSP90 for ligand binding, the data suggest that circadian GR signaling capacity is regulated in a region-specific pattern.
Authors:
A R Furay; E K Murphy; M P Mattson; Z Guo; J P Herman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  98     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-09     Completed Date:  2006-09-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1176-84     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, University of Cincinnati, College of Medicine, Ohio 45237-0506, USA. furayar@uc.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / blood
Animals
Brain Chemistry / physiology*
Cell Nucleus
Circadian Rhythm / physiology
Corticosterone / pharmacology
Cytosol / metabolism
HSP90 Heat-Shock Proteins / biosynthesis*
Hippocampus / metabolism
Hydrocortisone / blood
Hypothalamus / metabolism
Immunoblotting
Immunoprecipitation
Male
Radioimmunoassay
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid / metabolism*
Grant Support
ID/Acronym/Agency:
AG12962/AG/NIA NIH HHS; DK59803/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/HSP90 Heat-Shock Proteins; 0/Receptors, Glucocorticoid; 50-22-6/Corticosterone; 50-23-7/Hydrocortisone; 9002-60-2/Adrenocorticotropic Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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