Diphenyleneiodonium Inhibits Apoptotic Cell Death of Gastric Epithelial Cells Infected with Helicobacter pylori in a Korean Isolate
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초록
NADPH oxidase produces a large amount of reactive oxygen species (ROS) in Helicobacterpylori (H. pylori)-induced gastric epithelial cells. Even though ROS mediateapoptotic cell death, direct involvement of NADPH oxidase on H. pylori-inducedapoptosis remains unclear. Besides, H. pylori isolates show a high degree of genetic variability. The predominant genotype of H. pylori in Korea has been reportedas cagA+, vacA s1b, m2, iceA genotype. Present study aims to investigate whether NADPH oxidase-generated ROS mediate apoptosis in human gastric epithelialAGS cells infected with H. pylori in a Korean isolate. AGS cells were pretreatedwith or without an NADPH oxidase inhibitor diphenyleneiodonium (DPI) and cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1. Cell viability,hydrogen peroxide level, DNA fragmentation, and protein levels of p53, Bcl-2, and Bax were determined. Results showed that H. pylori inhibited cell viability with the density of H. pylori added to the cells. Inhibition of NADPH oxidase by DPI suppressed H. pylori-induced cell death, increased hydrogen peroxide, DNA fragmentation, and the ratio of Bax/Bcl-2, and p53 induction in AGS cells dose-dependently. The results suggest that targeting NADPH oxidase may prevent the developmentof gastric inflammation associated with H. pylori infection by suppressingabnormal apoptotic cell death of gastric epithelial cells.
Abstract
NADPH oxidase produces a large amount of reactive oxygen species (ROS) in Helicobacterpylori (H. pylori)-induced gastric epithelial cells. Even though ROS mediateapoptotic cell death, direct involvement of NADPH oxidase on H. pylori-inducedapoptosis remains unclear. Besides, H. pylori isolates show a high degree of genetic variability. The predominant genotype of H. pylori in Korea has been reportedas cagA+, vacA s1b, m2, iceA genotype. Present study aims to investigate whether NADPH oxidase-generated ROS mediate apoptosis in human gastric epithelialAGS cells infected with H. pylori in a Korean isolate. AGS cells were pretreatedwith or without an NADPH oxidase inhibitor diphenyleneiodonium (DPI) and cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1. Cell viability,hydrogen peroxide level, DNA fragmentation, and protein levels of p53, Bcl-2, and Bax were determined. Results showed that H. pylori inhibited cell viability with the density of H. pylori added to the cells. Inhibition of NADPH oxidase by DPI suppressed H. pylori-induced cell death, increased hydrogen peroxide, DNA fragmentation, and the ratio of Bax/Bcl-2, and p53 induction in AGS cells dose-dependently. The results suggest that targeting NADPH oxidase may prevent the developmentof gastric inflammation associated with H. pylori infection by suppressingabnormal apoptotic cell death of gastric epithelial cells.
참고문헌 (21)
- Clément MV, "Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: an hypothesis", Free Radic Res, 30, pp.247~252 (1999)
- Davies GR, "Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo", Gut, 35, pp.179~185 (1994)
- Nagata K, "Helicobacter pylori generates superoxide radicals and modulates nitric oxide metabolism", J Biol Chem, 273, pp.14071~14073 (1998)
- Bagchi D, "Production of reactive oxygen species by gastric cells in association with Helicobacter pylori", Free Radic Res, 24, pp.439~450 (1996)
- Kawahara T, "Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells", Am J Physiol Cell Physiol, 288, pp.C450~C457 (2005)
- Cha B, "HSP90beta interacts with Rac1 to activate NADPH oxidase in Helicobacter pylori-infected gastric epithelial cells", Int J Biochem Cell Biol, 42, pp.1455~1461 (2010)
- Cho SO, "Diphenyleneiodonium inhibits the activation of mitogen-activated protein kinases and the expression of monocyte chemoattractant protein-1 in Helicobacter pylori-infected gastric epithelial AGS cells", Inflamm Res, 60, pp.501~507 (2011)
- Jang SH, "Lycopene inhibits Helicobacter pylori-induced ATM", ATR-dependent DNA damage response in gastric epithelial AGS cells, 2012, pp.52, 607~615
- Labigne A, "Determinants of Helicobacter pylori pathogenicity", Infect Agents Dis, 5, pp.191~202 (1996)
- Mobley HL, "Defining Helicobacter pylori as a pathogen: strain heterogeneity and virulence", Am J Med, 100(5A), pp.2S~9S (1996)
- Seo JH, "Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-kappaB and induces chemokine expression in gastric epithelial AGS cells", Lab Invest, 84, pp.49~62 (2004)
- Kim MH, "Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts", Inflamm Res, 63, pp.347~356 (2014)
- Cho SO, "Signaling for integrin alpha5", beta1 expression in Helicobacter pylori-infected gastric epithelial AGS cells, 2006, pp.1090, 298~304
- Tominaga K, "Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach", Free Radic Biol Med, 43, pp.1627~1638 (2007)
- Keenan JI, "NADPH oxidase involvement in the pathology of Helicobacter pylori infection", Free Radic Biol Med, 38, pp.1188~1196 (2005)
- Jones RD, "NADPH oxidase: a universal oxygen sensor?", Free Radic Biol Med, 29, pp.416~424 (2000)
- Mori M, "Catalase and superoxide dismutase secreted from Helicobacter pylori", Helicobacter, 2, pp.100~105 (1997)
- Arslan D, "Is there an oxidative stress in children with Helicobacter pylori infection?", Saudi Med J, 28, pp.1222~1226 (2007)
- Morishita K, "Superoxide dismutase activity of Helicobacter pylori per se from 158 clinical isolates and the characteristics", Microbiol Immunol, 56, pp.262~272 (2012)
- Yuan X, "Activation of TLR4 signaling promotes gastric cancer progression by inducing mitochondrial ROS production", Cell Death Dis, 4, pp.e794~ (2013)
- Bauer G, "Helicobacter pylori protects oncogenically transformed cells from reactive oxygen species-mediated intercellular induction of apoptosis", Carcinogenesis, 35, pp.1582~1591 (2014)