title: Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells.
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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, P.O. Box 800708, Charlottesville, VA 22908-0708, USA.
authors.forename: Song-Ze
authors.initials: SZ
authors.lastname: Ding
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Minohara
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Fan
authors.forename: Jide
authors.initials: J
authors.lastname: Wang
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reyes
authors.forename: Janak
authors.initials: J
authors.lastname: Patel
authors.forename: Bernadette
authors.initials: B
authors.lastname: Dirden-Kramer
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.forename: Peter B
authors.initials: PB
authors.lastname: Ernst
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Crowe
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001706:Biopsy; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D002469:Cell Separation; D003593:Cytoplasm / Q000737:chemistry; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology*; D005753:Gastric Mucosa / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D044404:Genomic Islands; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D020169:Caspases