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KMID : 0352720200440010079
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Journal of Ginseng Research
2020 Volume.44 No. 1 p.79 ~ p.85
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Inhibitory effect of Korean Red Ginseng extract on DNA damage response and apoptosis in Helicobacter pylori?infected gastric epithelial cells
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Kang Hyun-Ju
Lim Joo-Weon
Kim Hye-Young
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Abstract
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Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori?induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori?infected gastric epithelial cells.
Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori?infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined.
Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori?infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori?infected gastric epithelial cells, similar to KRG.
Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori?infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.
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KEYWORD
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Apoptosis, Gastric epithelial cells, Helicobacter pylori, Panax ginseng
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