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


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.


CONCLUSIONS
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.
Nursing Policy and Research Institute, Biobehavioral Research Center, Yonsei University College of Nursing, Seoul, Korea.
Sang Hui
SH
Chu
Joo Weon
JW
Lim
Dong Goo
DG
Kim
Eung-Seok
ES
Lee
Kyung Hwan
KH
Kim
Hyeyoung
H
Kim
D000704:Analysis of Variance; D017209:Apoptosis; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015870:Gene Expression; D019254:Genes, bcl-2; D016158:Genes, p53; D016480:Helicobacter pylori; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein