Induction of gamma-glutamylcysteine synthetase by cigarette smoke is associated with AP-1 in human alveolar epithelial cells

FEBS Lett. 1996 Oct 28;396(1):21-5. doi: 10.1016/0014-5793(96)01027-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

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*
  • Glutamate-Cysteine Ligase / genetics
  • Glutamate-Cysteine Ligase / metabolism*
  • Glutathione / drug effects
  • Glutathione / metabolism
  • Humans
  • Promoter Regions, Genetic
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Smoke / adverse effects*
  • Transcription Factor AP-1 / drug effects
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • Antioxidants
  • RNA, Messenger
  • Recombinant Proteins
  • Smoke
  • Transcription Factor AP-1
  • Transcription Factors
  • Glutamate-Cysteine Ligase
  • Glutathione