Document Detail


Position 16 of the steroid nucleus modulates glucocorticoid-induced apoptosis at the transcriptional level in murine T-lymphocytes.
MedLine Citation:
PMID:  8937459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Synthetic glucocorticoids (GCs), which possess a different radical substituted in position 16 of the steroid nucleus structure, display various antiproliferative activities on activated lymphoid cells. We analysed this structure-function relationship between dexamethasone (DEX; methyl group in position 16 alpha) and beta-methasone (BM; methyl group in position 16 beta) with regard to two important aspects of GC activity, namely the activation of transcription and induction of apoptosis in IL-2-dependent murine lymphoid cells. DEX induced a higher percentage of apoptotic viable cells compared to BM. This structure-activity relationship was not related to differences in cytosolic glucocorticoid receptor (GR) affinity or kinetics of apoptosis. However, DEX was more efficient than BM in inducing transcriptional activation of an MMTV-CAT plasmid in transiently transfected CTLL-2 cells. In addition, DEX was more potent in inhibiting AP-1 DNA-binding activity compared to BM. These results suggest that the configuration in position 16 may influence the potency of GCs to induce apoptosis in lymphoid cells, mainly by modulating GR-induced transcription.
Authors:
M Perrin-Wolff; Z Mishal; J Bertoglio; M Pallardy
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  52     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1996-12-31     Completed Date:  1996-12-31     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1469-76     Citation Subset:  IM    
Affiliation:
Immunotoxicologie et Cancérogènese, CJF INSERM 93-01 Faculté de Pharmacie Paris-Sud, Châtenay-Malabry, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Betamethasone / chemistry,  metabolism,  pharmacology
Cell Line
DNA / metabolism
DNA Fragmentation
Dexamethasone / chemistry,  metabolism,  pharmacology
Glucocorticoids / chemistry*,  metabolism,  pharmacology*
Kinetics
Mice
Receptors, Glucocorticoid / metabolism
Structure-Activity Relationship
T-Lymphocytes / cytology,  drug effects*,  metabolism
Transcription Factor AP-1 / metabolism
Transcription, Genetic / drug effects
Transfection
Chemical
Reg. No./Substance:
0/Glucocorticoids; 0/Receptors, Glucocorticoid; 0/Transcription Factor AP-1; 378-44-9/Betamethasone; 50-02-2/Dexamethasone; 9007-49-2/DNA

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


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