Project/Area Number |
21390127
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Bacteriology (including Mycology)
|
Research Institution | Chiba University |
Principal Investigator |
NODA Masatoshi 千葉大学, 大学院・医学研究院, 教授 (60164703)
|
Co-Investigator(Kenkyū-buntansha) |
MORINAGA Naoko 千葉大学, 大学院・医学研究院, 准教授 (20092108)
SHIMIZU Takeshi 千葉大学, 大学院・医学研究院, 准教授 (70312840)
YAHIRO Kinnosuke 千葉大学, 大学院・医学研究院, 特任准教授 (80345024)
TSUTSUKI Hiroyasu 千葉大学, 大学院・医学研究院, 助教 (40586608)
|
Co-Investigator(Renkei-kenkyūsha) |
KUWABARA Satoshi 千葉大学, 大学院・医学研究院, 教授 (70282481)
MORI Masahiro 千葉大学, 大学院・医学研究院, 助教 (70345023)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
|
Keywords | 毒素 / ER ストレス / アポトーシス / 受容体 / 腸管出血性大腸菌 / サブチラーゼサイトトキシン / BiP / ERストレス / Bcl-2 / 志賀毒素 |
Research Abstract |
Subtilase cytotoxin (SubAB) is an AB5 cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum (ER) chaperone, BiP, leading to ER stress, which induces transient inhibition of protein synthesis and cell cycle arrest at G1 phase, and PERK-mediated Bax/Bak conformational change, cytochrome c release from mitochondria, followed by caspase-dependent apoptosis in mammalian cells. In addition, we showed in mice that SubAB induced small bowel hemorrhage and a coagulopathy characterized by thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time.
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