Document Detail

Induction of gamma-glutamylcysteine synthetase by cigarette smoke is associated with AP-1 in human alveolar epithelial cells.
MedLine Citation:
PMID:  8906859     Owner:  NLM     Status:  MEDLINE    
Increased levels of glutathione (GSH) occur in the epithelial lining fluid (ELF) of chronic cigarette smokers. Therefore we investigated the effect of cigarette smoke condensate solution (CSC) on GSH synthesis and the regulation of gamma-glutamylcysteine synthetase (gammaGCS) in human type II alveolar epithelial cells (A549). CSC exposure increased GSH levels, gammaGCS activity and gammaGCS heavy subunit (HS) mRNA, as well as increasing DNA binding of the activator protein-1 (AP-1) and the human antioxidant response element (hARE). Transfection of deletion constructs of the gammaGCS-HS promoter in a chloramphenicol acetyl transferase (CAT) reporter system revealed that an hARE, present within promoter, is not required for the CSC mediated induction. We conclude that CSC induction of gammaGCS-HS expression is associated with AP-1/AP-1-like responsive elements.
I Rahman; C A Smith; M F Lawson; D J Harrison; W MacNee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  396     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-01-09     Completed Date:  1997-01-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  21-5     Citation Subset:  IM    
Respiratory Medicine Unit, Department of Medicine, Rayne Laboratory, University of Edinburgh, UK.
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MeSH Terms
Antioxidants / pharmacology
Binding Sites
Bronchoalveolar Lavage Fluid / chemistry
Cells, Cultured
Dose-Response Relationship, Drug
Epithelial Cells / drug effects
Gene Expression Regulation / drug effects
Glutamate-Cysteine Ligase / drug effects*,  genetics,  metabolism*
Glutathione / drug effects,  metabolism
Promoter Regions, Genetic
Pulmonary Alveoli / cytology,  drug effects*,  metabolism
RNA, Messenger / biosynthesis,  drug effects
Recombinant Proteins / drug effects,  genetics,  metabolism
Sequence Deletion
Smoke / adverse effects*
Transcription Factor AP-1 / drug effects,  metabolism*
Transcription Factors / drug effects,  metabolism
Transcription, Genetic
Reg. No./Substance:
0/Antioxidants; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Smoke; 0/Transcription Factor AP-1; 0/Transcription Factors; 70-18-8/Glutathione; EC Ligase
Erratum In:
FEBS Lett 1997 Jul 14;411(2-3):393

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

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