2012 Fiscal Year Final Research Report
Analysis on multifunctional receptors for Helicobacter pylori VacA
| Project/Area Number |
22390084
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ISOMOTO Hajime 長崎大学, 病院, 准教授 (90322304)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ヘリコバクター・ピロリ / VacA / 細菌毒素 / 細菌毒素受容体 |
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| Research Abstract |
The pleiotropic effects of vacuolating cytotoxin (VacA) produced by Helicobacter pylori appear to result from activation of different signal transduction pathways through binding to several epithelial cell receptors, e.g., receptor protein tyrosine phosphatase (RPTP) β and α, and fibronectin. Here we purified from AZ-521 cells, a human gastric epithelial ell line, a surface membrane protein, p500, which binds VacA, and identified it as low-density lipoprotein receptor-related protein-1 (LRP1). LRP1 binding of VacA was shown to be specifically responsible for VacA-induced autophagy and apoptosis, but not activation of the Wnt/β-catenin signaling pathway. Similar to RPTPα and RPTP β, LRP1 mediates VacA internalization in AZ-521 cells, but in contrast to RPTPα and RPTP β, LRP1 targeted downstream pathways leading to autophagy and apoptosis. VacA-induced autophagy via LRP1 binding precedes apoptosis suggesting that an excessive autophagic activity can also lead to cell death. This is the first study to provide evidence that LRP1 mediates autophagy.
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[Journal Article] Low-density Lipoprotein Receptor-related Protein-1 (LRP1) Mediates Autophagy and Apoptosis Caused by Helicobacter pyloriVacA2012
Author(s)
Yahiro K, Satoh M, Nakano M, Hisatsune J, Isomoto H, Sap J, Suzuki H, Nomura F, Noda M, Moss J, Hirayama T.
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Journal Title
J Biol Chem.
Volume: 287
Pages: 3104-15
Peer Reviewed
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[Journal Article] Interweaving microRNAs and proinflammatory cytokines in gastric mucosa with reference to H. pylori infection.2012
Author(s)
Isomoto H, Matsushima K, Inoue N, Hayashi T, Nakayama T, Kunizaki M, Hidaka S, Nakayama M, Hisatsune J, Nakashima M, Nagayasu T, Nakao K, Hirayama T.
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Journal Title
J Clin Immunol
Volume: 32
Pages: 290-9
Peer Reviewed
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[Journal Article] Enhanced Expression of CXCL13 in Human Helicobacter pylori-Associated Gastritis2011
Author(s)
Nakashima Y, Isomoto H, Matsushima K, Yoshida A, Nakayama T, Nakayama M, Hisatsune J, Ichikawa T, Takeshima F, Hayashi T, Nakao K, Hirayama T, Kohno S
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Journal Title
Dig Dis Sci
Volume: 56
Pages: 2887-94
Peer Reviewed
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[Journal Article] Helicobacter pylori VacA reduces cellular expression of STAT3 and pro-survival Bcl-2 family proteins, Bcl-2 and Bcl-XL, leading to apoptosis in gastric epithelial cells.2011
Author(s)
Matsumoto A, Isomoto H, Nakayama M, Hisatsune J, Nishi Y, Nakashima Y, Matsushima K, Kurazono H, Nakao K, Hirayama T, and Kohno S
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Journal Title
Dig. Dis. Sci.
Volume: 56
Pages: 999-1006
Peer Reviewed
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[Journal Article] Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells.2010
Author(s)
Akada JK, Aoki H, Torigoe Y, Kitagawa T, Kurazono H, Hoshida H, Nishikawa J, Terai S, Matsuzaki M, Hirayama T, Nakazawa T, Akada R, Nakamura K.
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Journal Title
Dis. Model. Mech
Volume: 3
Pages: 605-17
Peer Reviewed
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[Presentation] Clinical significance of microRNAs in H.pylori-associated gastritis.2011
Author(s)
Kayoko Matsushima, Hajime Isomoto, Shigeru Kohno ,Yuko Akazawa ,Naoyuki Yamaguchi, Ken Ohnita, Tatsuki Ichikawa ,Fuminao Takeshima, Kazuhiko Nakano, Toshiya Hirayama
Organizer
The 8th Japan-Korea Joint Symposium on Helicobacter Infection
Place of Presentation
Seoul, Korea.
Year and Date
2011-05-29
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