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 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 H(2)O(2), 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.
Kimura
M
M
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, Nagasaki 852-8521, Japan.
Goto
S
S
Ihara
Y
Y
Wada
A
A
Yahiro
K
K
Niidome
T
T
Aoyagi
H
H
Hirayama
T
T
Kondo
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002460:Cell Line; D003603:Cytotoxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005753:Gastric Mucosa / Q000166:cytology; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori; C050159:gamma-glutamyl-glutathione; D006861:Hydrogen Peroxide; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D019803:Glutathione Disulfide