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Beta‐Carotene Inhibits Expression of Tumor Necrosis Factor Receptor‐Associated Factor 1 and Hyper‐Proliferation in Helicobacter pylori ‐Infected Gastric Epithelial Cells
Author(s) -
Park Yong Chae,
Lim Joo Weon,
Kim Hyeyoung
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb416
Subject(s) - helicobacter pylori , apoptosis , cell growth , tumor necrosis factor alpha , microbiology and biotechnology , gastric mucosa , biology , chemistry , cancer research , immunology , stomach , biochemistry , genetics
Hyper‐proliferation is observed in the mucosa of Helicobacter pylori‐(H. pylori) infected patients with adenocarcinoma. Tumor necrosis factor receptor‐associated factor 1 (TRAF1) is involved in cell survival and regulated by redox‐sensitive transcription factor NF‐kappa B. Overexpression of TARF1 by H. pylori promotes proliferation of gastric mucosal cells. The complex formed by TRAF1 interacts with inhibitor‐of‐apoptosis proteins (IAPs) such as cIAP1 and cIAP2, and thus mediates the anti‐apoptotic signals. Previously, we found that H. pylori activates NADPH oxidase to produce reactive oxygen species (ROS) and activate NF‐kappa B in gastric epithelial cells. We previously showed that beta‐carotene inhibits the expression of cyclooxygenase‐2 and inducible nitric oxide synthase by reducing ROS levels and NF‐kappa B activation in H. pylori ‐infected gastric epithelial cells. The purpose of the study is to determine whether beta‐carotene inhibits expression of TRAF1 by reducing ROS levels and suppresses cell proliferation in gastric epithelial cells infected with H. pylori treated with or without beta‐carotene. Human gastric epithelial AGS cells were infected with H. pylori strain NCTC11637 at the ratio of 1:50 (cell/bacterium). Beta‐carotene was dissolved in tetrahydrofuran and treated to the cells at final concentration of 0.5 and 1 microM. Cell proliferation was determined by viable cell numbers. mRNA and protein levels were determined by real time PCR analysis and western blotting. ROS levels were measured using DCF‐DA assay. As a result, H. pylori increased ROS levels and induced expression of TRAF1, cIAP1 and cIAP2 in AGS cells. H. pylori induced hyper‐proliferation of AGS cells. Beta‐carotene inhibited NADPH oxidase activation, hyper‐proliferation, and expression of TRAF1, cIAP1, and cIAP2, and reduced ROS levels in H. pylori ‐infected cells. In addition, both a known antioxidant N‐acetyl cysteine and an NADPH oxidase inhibitor diphenyleneiodonium inhibited H. pylori‐ induced TRAF1. In conclusion, consumption of beta‐carotene‐rich foods may be beneficial for inhibiting H. pylori‐ induced hyper‐proliferation of gastric epithelial cells by suppressing ROS‐mediated expression of TRAF1.