Chu Sang Hui, Lim Joo Weon, Kim Dong Goo, Lee Eung-Seok, Kim Kyung Hwan, Kim Hyeyoung
Nursing Policy and Research Institute, Biobehavioral Research Center, Yonsei University College of Nursing, Seoul, Korea.
Scand J Gastroenterol. 2011 Feb;46(2):148-55. doi: 10.3109/00365521.2010.525255. Epub 2010 Oct 24.
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.
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.
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.
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.
Bcl-2家族参与细胞凋亡的调控。根据细胞类型和刺激因素，NF-κB激活与Bcl-2的表达或Bcl-2的下调相关。此前，我们发现幽门螺杆菌（H. pylori）感染的胃上皮细胞中存在NF-κB激活、Bcl-2水平降低及细胞凋亡。本研究旨在探讨Bcl-2表达与NF-κB激活在幽门螺杆菌诱导AGS（胃腺癌）细胞凋亡性死亡中的关系。
用突变型IκBα转染AGS细胞以抑制NF-κB激活，或用Bcl-2基因转染以诱导Bcl-2过表达。测定Bcl-2、p53和Bax的mRNA表达、DNA片段化、细胞活力及凋亡细胞数量。
幽门螺杆菌诱导AGS细胞中Bcl-2在mRNA和蛋白质水平下降，但p53和Bax增加。与转染对照载体的细胞相比，转染突变型IκBα基因的细胞中幽门螺杆菌诱导的凋亡细胞增加及Bcl-2水平降低受到抑制。转染Bcl-2基因的细胞中，由凋亡细胞、DNA片段化和细胞活力测定的幽门螺杆菌诱导的凋亡受到抑制。
Bcl-2的下调由NF-κB激活介导，这可能是幽门螺杆菌感染的胃上皮细胞凋亡的潜在机制。
