Redox biology and gastric carcinogenesis: the role of Helicobacter pylori

Abstract

Almost half the world's population is infected by Helicobacter pylori (H. pylori). This bacterium increases the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human stomach, and this has been reported to impact upon gastric inflammation and carcinogenesis. However, the precise mechanism by which H. pylori induces gastric carcinogenesis is presently unclear. Although the main source of ROS/RNS production is possibly the host neutrophil, H. pylori itself produces O₂•⁻. Furthermore, its cytotoxin induces ROS production by gastric epithelial cells, which might affect intracellular signal transduction, resulting in gastric carcinogenesis. Excessive ROS production in gastric epithelial cells can cause DNA damage and thus might be involved in gastric carcinogenesis. Understanding the molecular mechanism of H. pylori-induced carcinogenesis is important for developing new strategies against gastric cancer.

Figure 1.

H. pylori-induced oxidative stress in stomach. LPS: lipopolysaccharide; NAP: neutrophil-activating protein; PMN: polymorphonuclear neutrophil; CagA: cytotoxin-associated gene A; PGN: peptidoglycan; MPO: myeloperoxidase; H₂O₂: hydrogen peroxide; NH₂Cl: monocloramine; OCl⁻: hypochlorite ion; NADP⁺/NADPH: nicotinamide adenine dinucleotide phosphate/reduced form of NADP⁺.

Figure 2.

Factors in H. pylori-induced gastric inflammation. cagPAI: cag pathogenicity island; VacA: vacuolating cytotoxin A; PicA: permit the induction of cytokines A; PicB: permit the induction of cytokines B; Tipα: tumor necrosis factorα inducing protein; SabA: sialic acid-binding adhesin A; CsrA: carbon storage regulator A; AhpC: alkyl hydroperoxide reductase C; Tpx: thiol-peroxidases; KatA: catalase A; SodB: superoxide dismutase B; fur: ferric uptake regulator; HSP: heat shock protein; MAPK: mitogen-activated protein kinase; MMP: matrix metalloproteinase; Shh: sonic hedgehog; IL-8: interleukin-8; IL-17: interleukin-17; iNOS: inducible nitric oxide synthase; NO: nitric oxide; TRX: thioredoxin; COX-1: cyclooxygenase-1; NADPH: nicotinamide adenine dinucleotide phosphate; Mox1: mitogen oxidase 1; 8OHdG: 8-hydroxy deoxyguanosine; SOD: superoxide dismutase; TBARS: thiobarbituric acid reactive substances; TNFα: tumor necrosis factor alpha; ROS: reactive oxygen species; NFκB: nuclear factor kappa B; CagA: cytotoxim associated gene A; NapA: neutrophil-activating protein A; Lps: lipopolysacharide; COX1: cyclokxygenare; NH₂Cl: monochloradine; ROS: reactive oxygen species; H₂P₂: hydrogen peroxide; OCl⁻: hypochloride ion.