論文 - 詳細
| RRC ID | 41556 |
|---|---|
| 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 | Gut |
| 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 Ikappabetaalpha 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 Ikappabetaalpha 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 | 50(6) |
| ページ | 771-8 |
| 公開日 | 2002-6-1 |
| DOI | 10.1136/gut.50.6.771 |
| PMID | 12010877 |
| PMC | PMC1773255 |
| MeSH | Adaptor Proteins, Signal Transducing* Apoptosis / physiology* Carrier Proteins / metabolism Caspase 8 Caspase 9 Caspase Inhibitors Caspases / metabolism Cell Communication / physiology Cell Survival / physiology Cytochrome c Group / metabolism* DNA Fragmentation / physiology Fas-Associated Death Domain Protein Helicobacter Infections / pathology* Helicobacter pylori / pathogenicity Helicobacter pylori / physiology* Humans Mitochondria / metabolism* NF-kappa B / metabolism* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Stomach Neoplasms / microbiology Stomach Neoplasms / pathology Tumor Cells, Cultured bcl-2-Associated X Protein bcl-X Protein fas Receptor / metabolism |
| IF | 19.819 |
| 引用数 | 58 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) HeLa(RCB0007) |