Helicobacter pylori protects oncogenically transformed cells from reactive oxygen species-mediated intercellular induction of apoptosis: Running head: Helicobacter pylori protects transformed cells

Abstract

Malignant transformation of gastric epithelial cells by chronic Helicobacter (H.) pylori infection is caused by several mechanisms including attraction of reactive oxygen species (ROS)-producing neutrophils and CagA-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 signaling pathways. H. pylori -associated catalase and superoxide dismutase (SOD) efficiently cooperate in the inhibition of HOCl and the NO/peroxynitrite signaling pathways. H. pylori catalase prevents HOCl synthesis through decomposition of hydrogen peroxide. H. 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 perse.