Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia.

Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia.
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短暂前脑缺血后成年大鼠脑中钙蛋白酶和半胱天冬酶活性的比较。

DOI:
10.1006/nbdi.2002.0526
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发表时间:
2002
影响因子:
6.1
通讯作者:
Neumar,RobertW
Neumar,RobertW
中科院分区:
医学1区
文献类型:
--
作者:
Zhang,Chen;Siman,Robert;Xu,YAnne;Mills,AngelaM;Frederick,JamesR;Neumar,RobertW

文献摘要

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钙蛋白酶和半胱天冬酶家族蛋白酶在缺血后神经元死亡中的作用仍有争议。本研究比较了短暂性前脑缺血10分钟后成年大鼠脑中钙蛋白酶和半胱天冬酶的时间、位置和相对活性。皮质、纹状体和海马匀浆的Western印迹显示α-血影蛋白裂解模式指示主要的钙蛋白酶活性,其在再灌注后24和48 h之间达到峰值。然而,免疫组织化学证据caspase 3激活和caspase介导的底物裂解检测早在1小时和迟至7天后,再灌注后在限定的神经元群体。还观察到同时或顺序的半胱天冬酶和钙蛋白酶激活,表明这些蛋白酶系统的相互作用的潜力。在这项研究中观察到的钙蛋白酶和半胱天冬酶活性的复杂时空模式提供了重要的见解的发展和评估的治疗策略,以减少蛋白酶介导的损伤后,全脑缺血。
The role of calpain and caspase family proteases in postischemic neuronal death remains controversial. This study compared the timing, location, and relative activity of calpains and caspases in the adult rat brain following 10 min of transient forebrain ischemia. Western blots of cortical, striatal, and hippocampal homogenates demonstrated a α-spectrin cleavage pattern indicative of predominant calpain activity, which peaked between 24 and 48 h after reperfusion. However, immunohistochemical evidence of both caspase 3 activation and caspase-mediated substrate cleavage was detected as early as 1 h and as late as 7 days after reperfusion in circumscribed neuronal populations. Simultaneous or sequential caspase and calpain activation was also observed suggesting the potential for interaction of these protease systems. The complex spatiotemporal pattern of calpain and caspase activity observed in this study provides important insights for the development and evaluation of therapeutic strategies to reduce protease-mediated injury following global brain ischemia.