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

The mechanism of the initiation ractions for the intrinsic blood coagulation,kinin release and fibrinolysis: the activation mechanism of the precursor of serine proteases by negatively-charged surfaces and gheir biological significance.

内在凝血、激肽释放和纤溶的起始反应机制：带负电表面的丝氨酸蛋白酶前体的激活机制及其生物学意义。

基本信息

批准号：
61480462
负责人：
KATO Hisao
金额：
$ 3.97万
依托单位：
National Cardiovascular Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480462/
关键词：
Blood coagulation initiation reaction kinin release 線溶系接触反応

项目摘要

The initiation reaction of the intrinsic blood coagulation is triggered by the interaction of a precursor of serine protease, Factor XII, with negativelycharged surfaces, which leads to the transformation of the precursor to active protease. This reaction is also the initiation reactions of the fibrinolytic system and kinin-releasing system. Although these reactions are considered to play important roles in the hemostasis, their biological significance remains to be established. This study was undertaken to clarify, (1) how the limited proteolysis of the precursors of serine proteases is caused after the interaction with negatively-charged surfaces and (2) what the biological significance of the activation reaction of Factor XII is.The results are as follows;(1) The initiation reactions of the intrinsic blood coagulation were reconstituted by the combination of ghe purified coagulation factors and the sensitive method to measure the activation of Factor XII was established. The activation reactions with kaolin, sulfatide and polysaccharide sulfate were found to be dependent not only on the concentrations of the surfaces and the coagulation factors, but also on the concentration of metal ions, particularly, zinc ion, and of sodium chloride. Platelets showed the strong inhibitory activity to the reactions by the interaction of the surfaces with the cationic proteins liberated from platelets.(2) We established the radioimmunoassay method for kininogens and andalyzed the kininogens (T-kininogens) which increased by the induction of inflammation using normal and HMW kininogen-deficient rats. We also analyzed the intrinsic blood coagulation and the activation of prekallikrein in the plasmas of rat, guineapig, ox, rabbit and sunkus, comparing with those of human plasma. We could find that some animals such as guinea-pig and rat are very sensitive in the activation of Factor XII and that some animals such as ox, rabbit and sunkus are very resistant in the actilvation.

内源性凝血的启动反应是由丝氨酸蛋白酶前体因子XII与带负电荷的表面相互作用而触发的，从而导致前体转化为活性蛋白酶。该反应也是纤溶系统和激肽释放系统的引发反应。虽然这些反应被认为在止血中发挥了重要作用，但它们的生物学意义仍有待确定。本研究旨在阐明(1)丝氨酸蛋白酶前体蛋白在与带负电的表面相互作用后发生有限的蛋白降解，以及(2)凝血因子XII的激活反应的生物学意义是什么。结果如下：(1)凝血因子的结合重组了内在凝血的启动反应，建立了检测凝血因子XII活性的灵敏方法。高岭土、硫脂和多糖硫酸酯的活化反应不仅依赖于表面浓度和凝血因子，而且还依赖于金属离子，特别是锌离子和氯化钠的浓度。我们建立了激肽原放射免疫分析方法，并用正常大鼠和HMW激肽原缺陷大鼠对炎症诱导后升高的激肽原(T激肽原)进行了分析。我们还分析了大鼠、豚鼠、牛、兔和Sunkus的血浆中的内源性凝血和前激肽释放酶的激活，并与人的血浆进行了比较。我们可以发现，有些动物如豚鼠和大鼠对FXII的激活非常敏感，而有些动物如牛、兔和Sunkus对FXII的激活非常抵抗。