| 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
|
| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2010: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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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 / VacA受容体 / 毒性発現 / 毒素作用 / 毒素受容体 / ピロリ菌 |
|---|
| 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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