Down-regulation of Bcl-2 is mediated by NF-κB activation in Helicobacter pylori- induced apoptosis of gastric epithelial cells
Nursing Policy and Research Institute, Biobehavioral Research Center, Yonsei University College of Nursing, Seoul, Korea. Scandinavian Journal of Gastroenterology
(Impact Factor: 2.36).
10/2010; 46(2):148-55. DOI: 10.3109/00365521.2010.525255
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.
Available from: Seung-Heon Hong
- "Moreover, Bcl-2 proteins control the release of mitochondrial cyt c by regulating mitochondrial permeability. Recent studies have shown that NF-κB acts upstream of apoptosis-related genes, including Bcl-2 . In this study, we found that treatment with an NO donor inhibited Bcl-2 expression. "
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ABSTRACT: Excessive nitric oxide (NO) production is toxic to the cochlea and induces hearing loss. However, the mechanism through which NO induces ototoxicity has not been completely understood. The aim of this study was to gain further insight into the mechanism mediating NO-induced toxicity in auditory HEI-OC1 cells and in ex vivo analysis. We also elucidated whether and how epigallocatechin-3-gallate (EGCG), the main component of green tea polyphenols, regulates NO-induced auditory cell damage. To investigate NO-mediated ototoxicity, S-nitroso-N-acetylpenicillamine (SNAP) was used as an NO donor. SNAP was cytotoxic, generating reactive oxygen species, releasing cytochrome c, and activating caspase-3 in auditory cells. NO-induced ototoxicity also mediated the nuclear factor (NF)-κB/caspase-1 pathway. Furthermore, SNAP destroyed the orderly arrangement of the 3 outer rows of hair cells in the basal, middle, and apical turns of the organ of Corti from the cochlea of Sprague-Dawley rats at postnatal day 2. However, EGCG counteracted this ototoxicity by suppressing the activation of caspase-3/NF-κB and preventing the destruction of hair cell arrays in the organ of Corti. These findings may lead to the development of a model for pharmacological mechanism of EGCG and potential therapies against ototoxicity.
PLoS ONE 09/2012; 7(9):e43967. DOI:10.1371/journal.pone.0043967 · 3.23 Impact Factor
Available from: Wei-Wen Chen
- "Monocyte-derived human dendritic cells release cytokines and increase expression of major histocompatibility class II proteins . Moreover, H. pylori infection can enhance cell proliferation ,  as to retrieve gastric mucosa damage and apoptosis of gastric epithelial cells , . Thus, to counteract H. pylori infection, host activates gene transcription involved in defense mechanism, inflammatory and immunological reaction, cell proliferation and apoptosis. "
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ABSTRACT: Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray using in vitro culture cells and in vivo gastric biopsies from patients of the Chronic Abdominal Complaint. To further explore the effects of H. pylori infection on host gene expression, we have collected the gastric antral mucosa samples from 6 untreated patients with gastroscopic and pathologic confirmation of chronic superficial gastritis. Among them three patients were infected by H. pylori and the other three patients were not. These samples were analyzed by a microarray chip which contains 14,112 cloned cDNAs, and microarray data were analyzed via BRB ArrayTools software and Ingenuity Pathways Analysis (IPA) website. The results showed 34 genes of 38 differentially expressed genes regulated by H. pylori infection had been annotated. The annotated genes were involved in protein metabolism, inflammatory and immunological reaction, signal transduction, gene transcription, trace element metabolism, and so on. The 82% of these genes (28/34) were categorized in three molecular interaction networks involved in gene expression, cancer progress, antigen presentation and inflammatory response. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Taken together, these data indicated that H. pylori infection could alter cellular gene expression processes, escape host defense mechanism, increase inflammatory and immune responses, activate NF-κB and Wnt/β-catenin signaling pathway, disturb metal ion homeostasis, and induce carcinogenesis. All of these might help to explain H. pylori pathogenic mechanism and the gastroduodenal pathogenesis induced by H. pylori infection.
PLoS ONE 03/2012; 7(3):e33030. DOI:10.1371/journal.pone.0033030 · 3.23 Impact Factor
Scandinavian Journal of Gastroenterology 02/2010; 45(2):131-2. DOI:10.3109/00365520903519636 · 2.36 Impact Factor
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