Down-regulation of Bcl-2 is mediated by NF-κB activation in Helicobacter pylori- induced apoptosis of gastric epithelial cells

Sang Hui Chua, Joo Weon Limb, Dong Goo Kimc, Eung-Seok Leed, Kyung Hwan Kimc & Hyeyoung Kim*ba Nursing Policy and Research Institute, Biobehavioral Research Center, Yonsei University College of Nursing, Seoul, Koreab Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, Koreac Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Koread College of Pharmacy, Yeungnam University, Gyeongsan, KoreaCorrespondence: Hyeyoung Kim, PhD, Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul 120-749, Korea. +82 2 2123 3125. +82 2 364 5781. kim626@yonsei.ac.kr Abstract Objective. Bcl-2 family is involved in the regulation of apoptosis. NF-κB activation is associated with either the expression of Bcl-2 or down-regulation of Bcl-2 depending on cell types and stimuli. Previously, we showed NF-κB activation, decrease in the level of Bcl-2, and apoptosis in Helicobacter pylori (H. pylori)-infected gastric epithelial cells. The present study aims to investigate the relation of Bcl-2 expression and NF-κB activation in H. pylori-induced apoptotic cell death of AGS (gastric adenocarcinoma) cells. Material and methods. AGS cells were transfected with mutant IκBα to suppress NF-κB activation or Bcl-2 gene to induce overexpression of Bcl-2. mRNA expression of Bcl-2, p53 and Bax, DNA fragmentation, cell viability, and the numbers of apoptotic cells were determined. Results. H. pylori induced decrease in Bcl-2, but increase in p53 and Bax at the levels of mRNA and protein in AGS cells. H. pylori-induced increment of apoptotic cells and decrease in Bcl-2 level were inhibited in the cells transfected with mutant IκBα gene as compared with the cells transfected with control vector. H. pylori-induced apoptosis determined by apoptotic cells, DNA fragmentation, and cell viability was inhibited in the cells transfected with Bcl-2 gene. Conclusion. Down-regulation of Bcl-2 is mediated by NF-κB activation, which may be the underlying mechanism of apoptosis in H. pylori-infected gastric epithelial cells.