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

Miyuki Kimura, Shinji Goto, Yoshito Ihara, Akihiro Wada, Kinnosuke Yahiro, Takuro Niidome, Haruhiko Aoyagi, Toshiya Hirayama, Takahito Kondo

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalMicrobial Pathogenesis
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • Glutathione
  • Glutathione metabolism
  • Helicobacter pylori
  • Oxidative stress
  • VacA

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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  • Cite this

    Kimura, M., Goto, S., Ihara, Y., Wada, A., Yahiro, K., Niidome, T., Aoyagi, H., Hirayama, T., & Kondo, T. (2001). Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori. Microbial Pathogenesis, 31(1), 29-36. https://doi.org/10.1006/mpat.2001.0446