Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells

Song Ze Ding, Yutaka Minohara, Jun Fan Xue, Jide Wang, Victor E. Reyes, Janak Patel, Bernadette Dirden-Kramer, Istvan Boldogh, Peter B. Ernst, Sheila E. Crowe

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

Helicobacter pylori infection is associated with altered gastric epithelial cell turnover. To evaluate the role of oxidative stress in cell death, gastric epithelial cells were exposed to various strains of H. pylori, inflammatory cytokines, and hydrogen peroxide in the absence or presence of antioxidant agents. Increased intracellular reactive oxygen species (ROS) were detected using a redox-sensitive fluorescent dye, a cytochrome c reduction assay, and measurements of glutathione. Apoptosis was evaluated by detecting DNA fragmentation and caspase activation. Infection with H. pylori or exposure of epithelial cells to hydrogen peroxide resulted in apoptosis and a dose-dependent increase in ROS generation that was enhanced by pretreatment with inflammatory cytokines. Basal levels of ROS were greater in epithelial cells isolated from gastric mucosal biopsy specimens from H. pylori-infected subjects than in cells from uninfected individuals. H. pylori strains bearing the cag pathogenicity island (PAI) induced higher levels of intracellular oxygen metabolites than isogenic cag PAI-deficient mutants. H. pylori infection and hydrogen peroxide exposure resulted in similar patterns of caspase 3 and 8 activation. Antioxidants inhibited both ROS generation and DNA fragmentation by H. pylori. These results indicate that bacterial factors and the host inflammatory response confer oxidative stress to the gastric epithelium during H. pylori infection that may lead to apoptosis.

Original languageEnglish (US)
Pages (from-to)4030-4039
Number of pages10
JournalInfection and immunity
Volume75
Issue number8
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Ding, S. Z., Minohara, Y., Xue, J. F., Wang, J., Reyes, V. E., Patel, J., Dirden-Kramer, B., Boldogh, I., Ernst, P. B., & Crowe, S. E. (2007). Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infection and immunity, 75(8), 4030-4039. https://doi.org/10.1128/IAI.00172-07