Document Detail

Recruitment of the p160 coactivators by the glucocorticoid receptor: dependence on the promoter context and cell type but not hypoxic conditions.
MedLine Citation:
PMID:  17481888     Owner:  NLM     Status:  MEDLINE    
In the nervous system, glucocorticoids exert beneficial or noxious effects, depending on their concentration and time-exposure. They act via the glucocorticoid receptor (GR) which recruits the p160 coactivators (SRC-1, SRC-2 and SRC-3). It was often shown that the three SRCs are interchangeable. The aim of the present study was to evaluate if the GR-SRCs interactions are dependent on several parameters like the target promoter structure, cell type or exogenous stressful parameters like hypoxia. We investigated the GR-SRCs interactions in two glial cells: astrocytes for the central nervous system and Schwann cells for the peripheral nervous system. We have shown by performing functional studies (overexpression and siRNA knock-down) that the recruitment of the three p160 by the GR is promoter-dependent and cell-specific. Moreover, we have shown that hypoxia (5% of oxygen) enhanced GR transactivation in both glial cells. Although hypoxia enhanced GR transactivation, it did not alter the interactions between the GR and the three p160s. Finally, we have shown that the potentiation of GR transactivation by hypoxia is due to an increase of the GR transcripts in Schwann cells but not in astrocytes. Altogether, these results reveal that the p160s are not interchangeable and that their recruitment by the GR is a multiparametric event.
Amalia Trousson; Julien Grenier; Cosima Fonte; Liliane Massaad-Massade; Michael Schumacher; Charbel Massaad
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Publication Detail:
Type:  Journal Article     Date:  2007-03-23
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  104     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-06-18     Completed Date:  2007-08-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  305-11     Citation Subset:  IM    
Inserm UMR788, Université Paris-Sud 11, 80, rue du Général Leclerc 94276 Le Kremlin-Bicêtre Cedex, France.
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MeSH Terms
Astrocytes / metabolism
Cell Hypoxia / physiology
Cells, Cultured
Histone Acetyltransferases / metabolism*
Nuclear Receptor Coactivator 1
Nuclear Receptor Coactivator 2 / metabolism*
Nuclear Receptor Coactivator 3
Organ Specificity*
Oxygen / pharmacology*
Promoter Regions, Genetic / physiology*
Protein Binding / drug effects
Rats, Sprague-Dawley
Receptors, Glucocorticoid / metabolism*
Schwann Cells / metabolism
Trans-Activators / metabolism*
Transcription Factors / metabolism*
Transcriptional Activation / drug effects
Reg. No./Substance:
0/Ncoa2 protein, rat; 0/Nuclear Receptor Coactivator 2; 0/Receptors, Glucocorticoid; 0/Trans-Activators; 0/Transcription Factors; 7782-44-7/Oxygen; EC Acetyltransferases; EC Receptor Coactivator 1; EC Receptor Coactivator 3

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

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