2005 Fiscal Year Final Research Report Summary
Mechanism of Helicobacter pylonVacAintoxication
| Project/Area Number |
16017280
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Nagasaki University |
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Principal Investigator |
HIRAYAMA Toshiya Nagasaki University, Institute of Tropical Medicine, Professor, 熱帯医学研究所, 教授 (50050696)
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| Co-Investigator(Kenkyū-buntansha) |
MASHIMA Hirosato The University of Tokyo Hospital, Research Associate, 医学部付属病院, 助手 (10261869)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Helicobacter pylori / vacuolating cytotoxin / VacA / Mechanism of intoxication |
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| Research Abstract |
Persistent infection with Helicobacter pylori causes chronic active gastritis, which predisposes the mucosa to peptic ulceration, and is believed to participate in the pathogenesis of gastric carcinoma and primary gastric lymphoma (i.e., mucosa-associated lymphoid tissue, or MALT type). Although H. pylori is a noninvasive bacterium that survives in the stomach mucosa, pathogenic strains of H. pylori produce and secrete a potent vacuolating cytotoxin, VacA.
In this study, we examined and analyzed following two subjects : 1) Identification of the extracellular sequence of the receptor required for VacA binding and clarification of toxin internalization, and 2) Mechanism of cell death caused by VacA.
Our results lead that
1)These data define the region in the RPTPO extracellular domain critical for VacA binding, in particular, the sequence QTTQP at positions 747-751 with crucial threonines at positions 748 and 749, and are consisitent with a role for terminal sialic acids, possibly due to threonine glycosylation.
VacA is concentrated in lipid rafts after binding to RPTP in non-lipid raft microdomains on AZ-521 cell surface. In addition, VacA-induced vacuolation as well as activation of p38 MAP kinase/ATF-2 (in submission).
2) VacA acts through different signaling pathways to induce apoptosis via Bax activation, independent of vacuolation.
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[Journal Article] Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic protein Bax, leading to cytochrome c release and cell death, independent of vacuolation2006
Author(s)
Yamasaki E., Wada A., Kumatori A., Nakagawa I., Funao J., Nakayama M., Hisatsune J., Kimura M., Moss J., Hirayama T.
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Journal Title
J. Biol. Chem. 281
Pages: 11250-11259
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPa and RPTPO, by Helicobacter pylori m2VacA.2005
Author(s)
De Guzman, B.B., Hisatsune, J., Nakayama, M., Yahiro, K., Wada, A., Yamasaki, E., Nishi, Y., Yamazaki, S., Azuma, T., Ito, Y., Ohtani, M., van der Wijk, T., den Hertog, J., Moss, M., Hirayama T.
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Journal Title
Cell Microbiol 7
Pages: 1285-293
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional antagonism between Helicobacter pylori CagA and VacA in control of the NFAT signaling pathway in gastric epithelial cells2005
Author(s)
Yokoyama, K., Higashi, H., Ishikawa, S., Fujii, Y., Kondo, S., Kato, H., Azuma, T., Wada, A., Hirayama, T., Aburatani, H., Hatakeyama, M.
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Journal Title
Proc. Natl. Acad. Sci. USA. 102
Pages: 9661-9666
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibitory effects of polyphenols on gastric injury by Helicobacter pylori VacA toxin.2005
Author(s)
Yahiro K, Shirasaka D, Tagashira M, Wada A, Morinaga N, Kuroda F, Choi 0, Inoue M, Aoyama N, Ikeda M, Hirayama T, Moss J, Noda M.
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Journal Title
Helicobacter. 10
Pages: 231-239
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Helicobacter pylori VacA activates the p38/ATF-2-mediated signal pathway in AZ-521 cells.2004
Author(s)
Nakayama, M., Kimura, M., Wada, A., Yahiro, K., Ogushi, 'K., Niidome, T., Fujikawa, A., Shirasaka, D., Aoyama, N., Kurazono, H., Noda, M., Moss, J., Hirayama, T.
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Journal Title
J. Biol. Chem. 279
Pages: 7024-7028
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Essential domain of receptor tyrosine phosphatase 3, RPTP0, for interaction with Helicobacter pylori vacuolating cytotoxin.2004
Author(s)
Yahiro, K., Wada, A., Yamasaki, E., Nakayama, M., Nishi, Y., Hisatsune, J., Morinaga, N., Sap, J., Noda, M., Moss, J., Hirayama, T.
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Journal Title
J. Biol. Chem. 299
Pages: 51013-51021
Description
「研究成果報告書概要(欧文)」より
