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

ArticleinScandinavian Journal of Gastroenterology 46(2):148-55 · October 2010with15 Reads
DOI: 10.3109/00365521.2010.525255 · Source: PubMed
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.
    • "A common regulator in these pathways is NFκB, which is up-regulated in such pathways in non-cancer conditions [44]. NFκB activation has been associated with the up-regulation of p53 and Bax expression but the down-regulation of Bcl-2 and survivin expression [45,46] . In addition, an IAP-IAP complex between survivin and XIAP was shown to increase the inhibition of caspase 3 activity and degradation of NFκBIa, with the consequent activation of NFκB [47,48]. "
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    • "Moreover, Bcl-2 proteins control the release of mitochondrial cyt c by regulating mitochondrial permeability. Recent studies have shown that NF-kB acts upstream of apoptosis-related genes, including Bcl-2 [52]. In this study, we found that treatment with an NO donor inhibited Bcl-2 expression. "
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    • "LPS, cagA, vacA), but also by pro-apoptotic and necrotic stimuli (ROS, RNS)707172. Several studies indicated that H. pylori-related gastric inflammation and cancer were associated with increased NF-kB activation [23,67,4,13] . In the present study, NFkB was an important central point in network 1(Figure 3). "
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