Document Detail


Correlation of membrane glucocorticoid receptor levels with glucocorticoid-induced apoptotic competence using mutant leukemic and lymphoma cells lines.
MedLine Citation:
PMID:  12244567     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the presence and functional implications of membrane glucocorticoid receptor (mGR) in several wild type (WT) and mutant mouse lymphoid cell lines (nuclear transfer decrease, NT(-); nuclear transfer increase, NT(i); and receptorless, R(-)). Direct fluorescent antibody staining revealed large aggregates of mGR-specific fluorescing antigens in the plasma membrane of the WT and mGR-enriched (mGR(++)) S-49 cells. While R(-) cells totally lacked mGR, this receptor level was low in NT(-) and NT(i) groups. FACS analysis corroborated these results, showing a approximately 4-10-fold difference between the highest mGR levels (mGR(++)) and the R(-) and NT(i) cells. Membrane extracts were analyzed for mGR by immunoblotting. Multiple receptor forms, ranging in M(r) from 94,000 to > 200,000, were observed in the WT cells, while only smaller peptides (85,000-94,000) were found in NT(-) cells. No detectable immunoreactive bands were identified in either membrane or cytosol immunoprecipitates of NT(i) and R(-) cell groups. Within 48 h post dexamethasone exposure > 98% of WT and mGR(++) S-49 cells underwent apoptosis, compared to 0-30% in the mutant cells, albeit the total receptor number is two to three times higher in NT(i) compared to WT. These results suggest a better correlation between the quantity and quality of mGRs (rather than total cellular GRs) and the ability of glucocorticoids (GCs) to lyse lymphoid cells.
Authors:
Bahiru Gametchu; Cheryl S Watson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  87     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2002  
Date Detail:
Created Date:  2002-09-23     Completed Date:  2003-03-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  133-46     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. gametchu@mcw.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*,  physiology
Binding Sites
Blotting, Western
Cell Membrane / metabolism
Centrifugation, Density Gradient / methods
Dexamethasone / pharmacology
Flow Cytometry
Fluorescent Antibody Technique, Direct
Glucocorticoids / pharmacology*
Humans
Immunoblotting
Leukemia / metabolism*,  pathology
Lymphoma / metabolism*,  pathology
Mice
Protein Binding
Receptors, Glucocorticoid / genetics,  metabolism*,  physiology
Statistics as Topic
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
65674//PHS HHS
Chemical
Reg. No./Substance:
0/Glucocorticoids; 0/Receptors, Glucocorticoid; 50-02-2/Dexamethasone

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


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