論文 - 詳細
| RRC ID | 61160 |
|---|---|
| 著者 | Maeda S, Yoshida H, Mitsuno Y, Hirata Y, Ogura K, Shiratori Y, Omata M. |
| タイトル | Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori. |
| ジャーナル | Mol Pathol |
| Abstract |
BACKGROUND AND AIMS:Although it is reported that Helicobacter pylori induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by H pylori have not yet been evaluated. METHODS:(1) H pylori strains (type 1 wild, TN2-deltacagE, TN2-deltavacA) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor IkappaBalpha were cocultured with H pylori, and cell viability and caspase activation were evaluated. NFkappaB regulated gene expression was also evaluated by ribonuclease protection assay. RESULTS:(1) Wild-type and deltavacA mutant H pylori induced apoptosis more potently than the deltacagE mutant. Inhibition of cell contact between H pylori and cancer cells and heat killing H pylori diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by H pylori as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by H pylori, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor IkappaBalpha that inhibits NFkappaB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. CONCLUSION:cag PAI positive H pylori is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation were also observed. |
| 巻・号 | 55(5) |
| ページ | 286-93 |
| 公開日 | 2002-10-1 |
| DOI | 10.1136/mp.55.5.286 |
| PMID | 12354930 |
| PMC | PMC1187257 |
| MeSH | Apoptosis* Caspases / metabolism Cell Survival Cytochrome c Group / metabolism DNA Fragmentation DNA, Neoplasm / genetics HeLa Cells Helicobacter Infections / metabolism Helicobacter Infections / pathology* Helicobacter pylori / pathogenicity* Humans Mitochondria / metabolism NF-kappa B / metabolism Neoplasm Proteins / metabolism Signal Transduction* Stomach Neoplasms / metabolism Stomach Neoplasms / microbiology* Stomach Neoplasms / pathology Tumor Cells, Cultured Virulence |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |