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Role of Calpain in Cerebral Vasospasm

钙蛋白酶在脑血管痉挛中的作用

基本信息

批准号：
02670642
负责人：
TANI Eiichi
金额：
$ 0.45万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670642/
关键词：
Vasospasm Calpain Actin Myosin Desmin Filamin Talin Vinculin gamma-Actinin カルパスタチン αーアクチニン Cキナ-ゼ Hー7 カルフォスチンC カルペプチン

项目摘要

Vasospasm was produced in the canine basilar artery by a two-hemorrhage method, whereas vasocontraction by a topical application of KCl or serotonin, and the experimental results with regard to calpain are as follows.1. Immunoblot analysis of mu-calpain in the basilar artery using antibodies against pre- and post-autolysis forms showed a continuous activation of mu- calpain in vasospasm and in contrast, a transient activation of mu-calpain only in the early stage of vasocontraction. Activities of calpastatin (endogenous inhibitor of calpain) was not changed in vasocontractin but significantly decreased in vasospasm, suggesting a proportional increase in calpain activities. 2. A topical treatment with calpeptin (selective inhibitor of calpain) was in-effective for vasocontraction but induced a dose-dependent dilation of the basilar artery in vasospasm.3. Immunoblot analysis of alpha-smooth muscle actin, myosin, desmin, filamin, talin, vinculin and alpha-actinin in the basilar artery demonstrated a severe progressive degradation of all proteins in vasospasm and only a slight degradation of myosin, filamin, talin and alpha-actinin in vasocontraction.In conclusion, it would be suggested that all intracellular devices responsible for the vascular smooth muscle contraction are degraded severely by calpain in vasospasm to induce resistance to therapy.

两出血法在犬基底动脉中产生血管痉挛，而局部应用KCl或5 -羟色胺使血管收缩，关于钙蛋白酶的实验结果如下。使用抗自溶前和自溶后形式的抗体对基底动脉中的mu-calpain进行免疫印迹分析显示，mu-calpain在血管痉挛中持续激活，相反，仅在血管收缩的早期阶段短暂激活。内源性钙蛋白酶抑制剂（calpastatin）的活性在血管收缩素中没有变化，但在血管痉挛中明显降低，提示钙蛋白酶活性成比例增加。2. 局部应用calpeptin （calpain的选择性抑制剂）治疗血管收缩无效，但会引起血管痉挛时基底动脉的剂量依赖性扩张。对基底动脉中α -平滑肌肌动蛋白、肌球蛋白、desmin、丝蛋白、talin、vculin和α -肌动蛋白的免疫印迹分析表明，血管痉挛时所有蛋白质都严重的进行性降解，而血管收缩时肌球蛋白、丝蛋白、talin和α -肌动蛋白只有轻微的降解。综上所述，所有负责血管平滑肌收缩的细胞内装置都被血管痉挛中的钙蛋白酶严重降解，从而诱导对治疗的抵抗。