title: Diphenyleneiodonium Inhibits Apoptotic Cell Death of Gastric Epithelial Cells Infected with Helicobacter pylori in a Korean Isolate.
abstract: NADPH oxidase produces a large amount of reactive oxygen species (ROS) in Helicobacter pylori (H. pylori)-induced gastric epithelial cells. Even though ROS mediate apoptotic cell death, direct involvement of NADPH oxidase on H. pylori-induced apoptosis remains unclear. Besides, H. pylori isolates show a high degree of genetic variability. The predominant genotype of H. pylori in Korea has been reported as cagA⁺, vacA s1b, m2, iceA genotype. Present study aims to investigate whether NADPH oxidase-generated ROS mediate apoptosis in human gastric epithelial AGS cells infected with H. pylori in a Korean isolate. AGS cells were pretreated with 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 development of gastric inflammation associated with H. pylori infection by suppressing abnormal apoptotic cell death of gastric epithelial cells.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Soon Ok
authors.initials: SO
authors.lastname: Cho
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea. kim626@yonsei.ac.kr.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002470:Cell Survival; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009861:Onium Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D056910:Republic of Korea; D013270:Stomach / Q000166:cytology / Q000382:microbiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D019255:NADPH Oxidases
keywords: Helicobacter pylori; NADPH oxidase; apoptosis; diphenyleneiodonium; gastric epithelial cells