RRC ID 12200
Author Rokutan K, Teshima S, Miyoshi M, Kawai T, Nikawa T, Kishi K.
Title Glutathione depletion inhibits oxidant-induced activation of nuclear factor-kappa B, AP-1, and c-Jun/ATF-2 in cultured guinea-pig gastric epithelial cells.
Journal J. Gastroenterol.
Abstract The aim of this study was to reveal the role of intracellular glutathione in the oxidative stress responses of gastric epithelial cells. Metabolic radiolabeling with L-[35S]methionine and analysis of synthesized proteins by gel electrophoresis and fluorography showed that upon exposure to hydrogen peroxide (H2O2) or diamide, primary cultures of guinea-pig gastric epithelial cells rapidly induced several undefined proteins, as well as heat shock proteins. When intracellular glutathione was depleted to less than 10% of the control value by treatment with buthionine-[S,R]-sulfoximine, these inductions were completely inhibited. Gel mobility shift assay demonstrated that H2O2 and diamide rapidly activated nuclear factor-kappa B (NF-kappaB), and diamide activated activator protein (AP)-1, and c-Jun/activating transcription factor (ATF)-2, suggesting that the response may be coupled to these reduction-oxidation (redox)-sensitive transcription factors, as well as heat shock transcription factor 1. The activations of NF-kappaB, AP-1, and c-Jun/ATF-2 by the oxidants did not occur in glutathione-depleted cells. Northern blot analysis showed that glutathione depletion markedly or completely suppressed the diamide-induced expression of c-fos and c-jun mRNAs. These results suggest that intracellular glutathione redox may participate in the initiation of oxidative stress responses; thereby, it plays an important role in gastric mucosal defense.
Volume 33(5)
Pages 646-55
Published 1998-10
PMID 9773928
MeSH Activating Transcription Factor 2 Animals Blotting, Northern Cells, Cultured Cyclic AMP Response Element-Binding Protein / metabolism* DNA Primers Epithelial Cells / metabolism* Gastric Mucosa / cytology Gastric Mucosa / metabolism* Glutathione / metabolism* Guinea Pigs Male NF-kappa B / metabolism* Oxidative Stress* Proto-Oncogene Proteins c-jun / metabolism* Transcription Factor AP-1 / metabolism* Transcription Factors / metabolism*
IF 5.561
Times Cited 24
DNA material pBS rcjun-1 Rat c-Jun protooncogene (RDB01130)