权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on the toxic action of cytolethal toxin from Clostridium septicum.

败血梭菌细胞致死毒素的毒性作用研究。

基本信息

批准号：
16580256
负责人：
MUKAMOTO Masafumi
金额：
$ 2.11万
依托单位：
Osaka Prefecture University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16580256/
关键词：
Clostridium septicum cytolethal toxin cholesterol raft GPI-anchored protein actin heart failure 心臓細胞傷害

项目摘要

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.

测定了不同动物红细胞中败血症梭菌α毒素的活性。结果表明，α -毒素的溶血活性与多种动物中gpi锚定蛋白亚群的特异性红细胞膜蛋白相关。我用小鼠结缔组织细胞系L-929研究了α -毒素寡聚物在哺乳动物细胞上形成的分子机制。原毒素在非筏体中与gpi锚定蛋白结合，被细胞表面蛋白酶激活后，被激活的毒素移动到脂质筏上并寡聚形成孔。研究还表明，胆固醇在α -毒素寡聚和细胞毒性中起着重要作用。α -肌动蛋白是一种新的毒素结合蛋白，为阐明脓毒杆菌感染引起的恶性水肿等特殊症状提供了一些信息。恶性水肿是肌肉组织的一种疾病，导致死亡的最终原因是心力衰竭。我证明了α -毒素与α -肌动蛋白结合在细胞膜上并形成孔后特异性地相互作用。结果表明，接种α毒素后，小鼠原代心肌细胞和大鼠灌注心脏均立即停止心跳，但未出现心肌坏死。提示α毒素诱导心脏骤停的机制并非细胞坏死。未来，我将在分子和细胞水平上估计心力衰竭与α毒素与肌动蛋白结合之间的相关性。