Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori

Helicobacter pylori vacuolating cytotoxin (VacA) is believed to be one of t he factors that induces gastric disease. Our previous study indicated that VacA causes a decrease in the intracellular ATP level in human gastric epit helial cells, suggesting to impair mitochondrial membrane potential followe d by a decrease in energy metabolism (Kimura et al., Microb. Pathog., 1999, 26. 45-52). In the present study, we investigated whether the decrease in ATP level affects glutathione metabolism, in which its synthesis and efflux are ATP-dependent. Treatment of AZ-521 human gastric epithelial cells with 120 nM VacA for 6 h suppressed the afflux of oxidized glutathione (GSSG) i n a dose-and time-dependent manner. The efflux of GSSG from the cells and g lutathione (GSH) synthesis of cells treated with VacA were approximately 50 and 70% of those of the control, respectively. The turnover rate of intrac ellular GSH was also suppressed by VacA. Viability of the cells pretreated with VacA, then further incubated with H2O2, was decreased by 50% at 6 h an d 70% at 12 h. These results suggested that VacA impairs GSH metabolism in the gastric epithelial cells, which weakens the resistance of the cells aga inst oxidative stress or cellular redox regulation by GSH. (C) 2001 Academi c Press.