TY - JOUR
T1 - Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori
AU - Kimura, Miyuki
AU - Goto, Shinji
AU - Ihara, Yoshito
AU - Wada, Akihiro
AU - Yahiro, Kinnosuke
AU - Niidome, Takuro
AU - Aoyagi, Haruhiko
AU - Hirayama, Toshiya
AU - Kondo, Takahito
N1 - Funding Information:
This work was supported by a grant in aid from the Ministry of Education, Science and Culture of Japan. The authors thank Dr Y. Urata (Department of Biochemistry and Molecular Biology in Disease, Nagasaki University, School of Medicine) and Dr I. Kato (Medical School of Chiba University) for fruitful discussions.
PY - 2001
Y1 - 2001
N2 - Helicobacter pylori vacuolating cytotoxin (VacA) is believed to be one of the factors that induces gastric disease. Our previous study indicated that VacA causes a decrease in the intracellular ATP level in human gastric epithelial cells, suggesting to impair mitochondrial membrane potential followed 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 efflux of oxidized glutathione (GSSG) in a dose-and time-dependent manner. The efflux of GSSG from the cells and glutathione (GSH) synthesis of cells treated with VacA were approximately 50 and 70% of those of the control, respectively. The turnover rate of intracellular 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 and 70% at 12 h. These results suggested that VacA impairs GSH metabolism in the gastric epithelial cells, which weakens the resistance of the cells against oxidative stress or cellular redox regulation by GSH.
AB - Helicobacter pylori vacuolating cytotoxin (VacA) is believed to be one of the factors that induces gastric disease. Our previous study indicated that VacA causes a decrease in the intracellular ATP level in human gastric epithelial cells, suggesting to impair mitochondrial membrane potential followed 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 efflux of oxidized glutathione (GSSG) in a dose-and time-dependent manner. The efflux of GSSG from the cells and glutathione (GSH) synthesis of cells treated with VacA were approximately 50 and 70% of those of the control, respectively. The turnover rate of intracellular 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 and 70% at 12 h. These results suggested that VacA impairs GSH metabolism in the gastric epithelial cells, which weakens the resistance of the cells against oxidative stress or cellular redox regulation by GSH.
KW - Glutathione
KW - Glutathione metabolism
KW - Helicobacter pylori
KW - Oxidative stress
KW - VacA
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U2 - 10.1006/mpat.2001.0446
DO - 10.1006/mpat.2001.0446
M3 - Article
C2 - 11427034
AN - SCOPUS:0034931859
SN - 0882-4010
VL - 31
SP - 29
EP - 36
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
IS - 1
ER -
