Suppression of glutathione transferase P expression by glucocorticoid

Biochem Biophys Res Commun. 1992 Sep 16;187(2):976-83. doi: 10.1016/0006-291x(92)91293-y.

Abstract

A strong enhancer element, GPEI, of the glutathione transferase P gene (GST-P) gene is composed of two phorbol 12-O-tetradecanoate 13-acetate (TPA) responsive element (TRE)-like sequences at opposite orientation. Unlike TRE sequences of other genes, GPEI exhibits a strong enhancer activity in F9 cells, which contains little AP-1. GPEI bound to AP-1 In vitro and GST-P expression was activated by TPA and exogenously introduced c-jun gene in a rat fibroblast cell line. Both the stimulated expression of GST-P gene by TPA and that by over-expressed c-Jun were suppressed to the basal level by dexamethasone, an inhibitor of AP-1. Basal expression of GST-P gene, however, was not inhibited by dexamethasone. Transfected chloramphenicol acetyltransferase (CAT) gene having GPEI also behaved as the endogenous GST-P gene. These results indicate that the GPEI is activated by AP-1 but constitutive activity of this enhancer in a rat fibroblast cell line 3Y1 cells is due to some unknown mechanism other than AP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Dexamethasone / pharmacology*
  • Enhancer Elements, Genetic
  • Fibroblasts / metabolism
  • Gene Expression / drug effects*
  • Glutathione Transferase / genetics*
  • Macromolecular Substances
  • Molecular Sequence Data
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection

Substances

  • Macromolecular Substances
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Dexamethasone
  • Chloramphenicol O-Acetyltransferase
  • Glutathione Transferase
  • Tetradecanoylphorbol Acetate