| Research Abstract |
In studies with the use of cultured rat gastric mucosal and endothelial cells, we have demonstrated that (1) diethyldithiocarbamate dose-dependently enhanced hydrogen peroxide (H_2O_2) -induced damage to gastric cells, corresponding with inhibition of endogenoud SOD activity ; (2) extracellular glutahione (GSH) potects gastric cells from H_2O_2by accelerating intracellular GSH synthesis ; this is mediated by gamma-glutamyl transpcptidase acting on extracellular GSH (which supplies these cells with cysteine) and then by intracellular gamma-glutamylcysteine synthelase, a mechanism of GSH uptake distinctly different from that of intestinal cells ; (3) oxidant stress causes lipid peroxidation of gastric cells, which is then followed by cytolysis, and iron chelation protccls cells from oxidant stress presumably through inhibition of lipid peroxidation ; (4) GSH isopropylester also protccts gastric cclls from oxidant throuhg inihibition of lipid peroxidation, by an uptake mechanism similar to that of native GSH ; (5) monochloramine (NH_2Cl), which could be threoretically produced in Helicobacter pylori infection-associated inflammation, is more toxic to gastric cells than H_2O_2, and intracellular GSH plays a role as a potent defense system against NH_2Cl ; and (6) ethanol induces superoxide generation by gastric cells, and inhibition of the GSH-redox cycle aggravates ethanol damage ; such phenomena cannot be observed in endothelial cells, and (7) the mechanisms by which oxidant stress induces cytolysis of gastric cells, postulated by the prineipal investigator, is essentially similar to those of endothelial cells.
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