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 1998-10-1
DOI 10.1007/s005350050151
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 6.132
Times Cited 27
DNA material pBS rcjun-1 Rat c-Jun protooncogene (RDB01130)