NF-kappaB and Bcl-2 in Helicobacter pylori-induced apoptosis in gastric epithelial cells.
Helicobacter pylori (H. pylori) has been considered as an important pathogen of gastroduodenal inflammation and gastric carcinogenesis. However, the pathogenic mechanisms including H. pylori-induced apoptosis and subsequent molecular mechanisms have not been clarified yet. The present study examined the role of Bcl-2 and its relation to NF-kappaB in H. pylori-induced apoptosis in human gastric epithelial AGS cells. AGS cells were cultured in the presence of H. pylori, at a bacterium/cell ratio of 300:1, for the determination of apoptosis, NF-kappaB activation with IkBa degradation, and Bcl-2 level. AGS cells were transfected with a control vector (pCMV cells) or a full-length human Bcl-2 expression vector (Bcl-2 cells). H. pylori-induced apoptosis and NF-kappaB activation were compared in the wild-type cells and the transfected cells. As a result, H. pylori increased apoptotic cells with chromatin condensation and reduced Bcl-2 levels, which were accompanied with NF-kappaB activation. H. pylori induced sixfold increase in the number of apoptotic cells in wild-type cells and pCMV cells. H. pylori-induced increment of apoptotic cells were relatively lower in Bcl-2 cells than pCMV cells. H. pylori-induced NF-kappaB activation and IkBa degradation were not different in the wild-type cells, pCMV cells, and Bcl-2 cells. In conclusion, the reduced gastric Bcl-2 level may be the main pathogenic mechanism of H. pylori-induced apoptosis in gastric epithelial cells.
Chu
Sang Hui
SH
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Lim
Joo Weon
JW
Kim
Kyung Hwan
KH
Kim
Hyeyoung
H
D000230:Adenocarcinoma; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013274:Stomach Neoplasms; D014162:Transfection
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins