Protection of cultured gastric cells against tert-butyl hydroperoxide by glutathione isopropyl ester.
Oxidants are involved in the pathogenesis of a variety of gastrointestinal disorders. Intracellular GSH protects rat gastric cells against oxidants. We examined whether GSH isopropyl ester (GSH ester) can protect against oxidants and whether a system of GSH ester uptake is present in these cells; we also investigated a possible role of GSH in inhibiting lipid peroxidation. Cytotoxicity was quantified by 51Cr release. Lipid peroxidation was assessed by measuring malondialdehyde production. tert-Butyl hydroperoxide caused a dose-dependent increase in 51Cr release. Treatment with GSH ester attenuated the toxicity of tert-butyl hydroperoxide. Incubation with GSH ester enhanced the cellular GSH content, which was prevented by DL-buthionine-[S,R]-sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase. GSH ester prevented tert-butyl hydroperoxide-induced lipid peroxidation, corresponding with the degree of protection. Therefore, we concluded that GSH isopropyl ester protects gastric cells against oxidants through the accumulation of intracellular GSH. This protection is mediated in part by the prevention of hydroperoxide-induced lipid peroxidation. However, the gastric epithelial system of GSH ester uptake appears distinctly different from those observed in hepatocytes, lymphoid cells and fibroblasts in terms of mediation of gamma-glutamylcysteine synthetase activity.
Second Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
N
N
Yamaguchi
N
N
Yajima
M
M
Ishida
T
T
Shimada
H
H
Hiraishi
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D002860:Chromium Radioisotopes; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D020122:tert-Butylhydroperoxide; C058293:glutathione monoisopropyl ester; D005978:Glutathione