Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains
Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains
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DOI：
10.1016/s0014-5793(00)02431-5
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发表时间：
2001-01-26
期刊：
影响因子：
3.5
通讯作者：
Hasegawa, M
中科院分区：
文献类型：
--
作者：
Taniguchi, S;Fujita, Y;Hasegawa, M
阿尔茨海默病神经原纤维缠结中的 Tau 已被证明过度磷酸化，CDK5、GSK3、MAP 激酶和 SAP 激酶是 tau 磷酸化的候选激酶。最近，据报道，在阿尔茨海默病（AD）大脑中，CDK5 激活剂 p35 向 p25 的转化上调，并且 p35 被钙蛋白酶裂解产生 p25。我在这里证明，在大鼠和人类大脑中，p35 在死后短时间内迅速裂解为 p25，并且 p35 到 p25 的转化部分依赖于钙蛋白酶活性。对 AD 患者或年龄匹配的对照个体（死后短暂延迟）制备的大脑进行免疫印迹分析，发现 AD 大脑中的 p25 水平没有特异性增加，而与对照相比，AD 大脑中的活性钙蛋白酶水平仅增加。这些观察结果表明，p35 向 p25 的转化是死后降解事件，并且在 AD 大脑中可能不会上调。 (C) 2001 年欧洲生化学会联合会。由 Elsevier Science B.V. 出版。保留所有权利。
Tau in Alzheimer neurofibrillary tangles has been shown to be hyperphosphorylated and CDK5, GSK3, MAP kinase and SAP kinases are the candidate kinases for the phosphorylation of tau. Recently, it was reported that the conversion of p35, the activator of CDK5, to p25 was upregulated in Alzheimer's disease (AD) brains, and that p35 is cleaved to yield p25 by calpain. Here me show that p35 is rapidly cleaved to p25 in rat and human brains within a short postmortem delay and that the conversion of p35 to p25 is partially dependent on calpain activity. Immunoblot analysis of brains prepared from patients with AD or age-matched control individuals with a short postmortem delay revealed no specific increase in the levels of p25 in AD brains, whereas the levels of active form of calpain mere increased in AD brains compared to the those in controls. These observations suggest that the conversion of p35 to p25 is a postmortem degradation event and may not be upregulated in AD brains. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.