title: Helicobacter pylori protects oncogenically transformed cells from reactive oxygen species-mediated intercellular induction of apoptosis.
abstract: Malignant transformation of gastric epithelial cells by chronic Helicobacter pylori infection is caused by several mechanisms including attraction of reactive oxygen species (ROS)-producing neutrophils and cytotoxin-associated antigen A-mediated dysplastic alterations. Here we show that H.pylori protects transformed cells from ROS-mediated intercellular induction of apoptosis. This potential control step in oncogenesis depends on the HOCl and NO/peroxynitrite (PON) signaling pathways. Helicobacter pylori-associated catalase and superoxide dismutase (SOD) efficiently cooperate in the inhibition of HOCl and the NO/PON signaling pathways. Helicobacter pylori catalase prevents HOCl synthesis through decomposition of hydrogen peroxide. Helicobacter pylori-associated SOD interferes with the crucial interactions between superoxide anions and HOCl, as well as superoxide anions and NO. The ratio of bacteria to malignant cells is critical for sufficient protection of transformed cells. Low concentrations of H.pylori more efficiently inhibited ROS-mediated destruction of transformed cells when compared with high concentrations of bacteria. Our data demonstrate the critical role of H.pylori antioxidant enzymes in the survival of transformed cells, modulating an early step of oncogenesis that is distinct from the transformation process per se.
authors.affiliation: Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg D-79104, Germany, Institute of Medical Microbiology, Charité, Berlin D-12203, Germany and Institute of Immunology and Institute of Microbiology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg D-79104, Germany georg.bauer@uniklinik-freiburg.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Bauer
authors.affiliation: Institute of Medical Microbiology, Charité, Berlin D-12203, Germany and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Institute of Immunology and.
authors.forename: Peter
authors.initials: P
authors.lastname: Aichele
authors.affiliation: Institute of Microbiology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg D-79104, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Glocker
mesh_terms: D000818:Animals; D017209:Apoptosis; D002374:Catalase; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005354:Fibrosarcoma / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016877:Oxidants; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase