| Project/Area Number |
16580256
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
MUKAMOTO Masafumi Osaka Prefecture University, Graduate school of life and environmental sciences, Associate Professor, 生命環境科学研究科, 助教授 (80231629)
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| Co-Investigator(Kenkyū-buntansha) |
KOZAKI Shunji Osaka Prefecture University, Graduate school of life and environmental sciences, Professor, 生命環境科学研究科, 教授 (10109895)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Clostridium / septicum / cytolethal toxin / cholesterol / raft / GPI-anchored protein / actin / heart failure / 心臓 / 細胞傷害 |
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| Research Abstract |
The activity of Clostridium septicum alpha-toxin was determined in erythrocytes of various animals. It was shown that hemolytic activities of alpha-toxin associated with specific erythrocyte membrane proteins that were subsets of GPI-anchored proteins in various animal species. I examined molecular mechanisms of oligomer formation of alpha-toxin on mammalian cells using mouse connective tissue cell line, L-929. After the protoxin binds to GPI-anchored proteins in non-raft for activation by cell surface protease, activated toxin moves to lipid raft and oligomerizes leading to pore-formation. It was also shown that cholesterol played a significant role in alpha-toxin oligomerization and cytotoxicity. Alpha-actin was identified as a new toxin-binding protein, which provided some information to elucidate peculiar symptoms such as malignant edema involving C.septicum infection. Malignant edema is a disease condition of muscle tissues and the ultimate cause of the death is heart failure. I proved that alpha-toxin specifically interact with alpha-actin after binding to cell membrane and pore formation. It was observed that the heart beat has immediately stopped in primary mouse cardiac cells and rat perfused heart without necrosis after inoculation of alpha-toxin. These results indicate that alpha-toxin can induce cardiac arrest with the other mechanism than cell necrosis. In future, I will estimate relevances between heart failure and binding of alpha-toxin to actin in molecular and cellular level.
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