Up- and down-regulation of calpain inhibitor polypeptide, calpastatin, in postischemic hippocampus
Up- and down-regulation of calpain inhibitor polypeptide, calpastatin, in postischemic hippocampus
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缺血后海马中钙蛋白酶抑制剂多肽、钙蛋白酶抑制素的上调和下调
DOI：
10.1016/s0304-3940(97)00309-1
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发表时间：
1997
影响因子：
2.5
通讯作者：
M. Yokota
中科院分区：
文献类型：
--
作者：
T. Saido;S. Kawashima;E. Tani;M. Yokota
基于我们以前的观察，短暂前脑缺血诱导钙蛋白酶催化的蛋白水解在沙鼠海马在区域特异性的方式，我们研究了缺血的影响，内源性钙蛋白酶特异性抑制剂蛋白，钙蛋白酶抑制剂，在组织中的数量和定位。短暂（5分钟）前脑缺血再灌注诱导海马，特别是锥体细胞，在4小时内的钙蛋白酶抑制蛋白免疫反应性的整体增加，通过Western印迹和免疫组织化学分析。钙蛋白酶抑制蛋白的量，但是，减少到缺血前的水平和较低的24小时至7天，由于蛋白水解，除了在CA2显示持续升高的钙蛋白酶抑制蛋白免疫反应。因为钙蛋白酶抑制剂不仅是一种有效的抑制剂，而且也是钙蛋白酶的首选底物，因为CA2神经元比邻近的CA1神经元更不容易受到缺血应激的影响，这些观察结果意味着钙蛋白酶抑制剂参与钙蛋白酶调节作为诱饵底物，并可能参与缺血条件下的神经保护。钙蛋白酶抑制蛋白可能与热休克蛋白等已知的缺血诱导应激蛋白共同参与应激反应。
Based on our previous observation that transient forebrain ischemia induces calpain-catalyzed proteolysis in gerbil hippocampus in a region-specific manner, we examined the effect of ischemia on the quantity and localization of the endogenous calpain-specific inhibitor protein, calpastatin, in the tissue. Brief (5 min) forebrain ischemia followed by reperfusion induced an overall increase of calpastatin immunoreactivity in hippocampus, particularly in pyramidal cells, in 4 h as analyzed by Western blotting and immunohistochemistry. The amount of calpastatin, however, decreased to the preischemic level and lower in 24 h to 7 days due to proteolysis except in CA2 showing continuously elevated calpastatin immunoreactivity. Because calpastatin is not only a potent inhibitor but also a preferred substrate for calpain and because CA2 neurons are less vulnerable to ischemic stress than the adjacent CA1 neurons, these observations imply involvement of calpastatin in calpain regulation as a bait substrate and, possibly, in neuroprotection under ischemic conditions. Calpastatin may participate in the stress responses together with the previously known ischemia-induced stress proteins such as heat shock proteins.