Calpain and N-methyl-D-aspartate (NMDA)-induced excitotoxicity in rat retinas
Calpain and N-methyl-D-aspartate (NMDA)-induced excitotoxicity in rat retinas
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DOI：
10.1016/j.brainres.2005.04.016
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发表时间：
2005-06-07
期刊：
影响因子：
2.9
通讯作者：
Kwong, JMK
中科院分区：
文献类型：
--
作者：
Chiu, K;Lam, TT;Kwong, JMK
钙蛋白酶介导的蛋白水解是中枢神经系统急性损伤和慢性神经退行性疾病中神经细胞死亡的主要过程。然而，钙蛋白酶的激活在兴奋性毒性神经元死亡的早期阶段也起着保护作用。钙蛋白酶在N-甲基-D-天冬氨酸（NMDA）暴露后神经元死亡和恢复中的确切作用尚不清楚。本研究的目的是检查参与的mu和m-钙蛋白酶NMDA诱导的兴奋性毒性在成年大鼠视网膜。在RGC层细胞和内核层细胞中，Mu-calpain的免疫反应性增加，在注射NMDA后12 h达到最大表达。这一点用蛋白质印迹法进一步证实。TdT介导的生物素-dUTP缺口末端标记（TUNEL）阳性细胞与中度或强烈的μ-钙蛋白酶免疫反应性共同定位在视网膜内层。相比之下，在注射NMDA后的任何时间点，m-钙蛋白酶免疫反应性没有显着变化。同时注射2 nmol的钙蛋白酶抑制剂（钙蛋白酶抑制剂II）显着减少TUNEL阳性细胞的数量在视网膜内层NMDA注射后18小时和保存的RGC样细胞计数在注射后7天。本研究结果表明，p-钙蛋白酶可能参与介导NMDA诱导的大鼠视网膜兴奋性毒性，钙蛋白酶抑制剂可能在NMDA相关疾病中发挥治疗作用。(c)2005 Elsevier B. V.保留所有权利。
Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death in both acute insults and the chronic neurodegenerative disorders in the central nerves system. However, activation of calpain also plays a protective function in the early phase of excitotoxic neuronal death. The exact role of calpains in neuronal death and recovery after exposure to N-methyl-D-aspartate (NMDA) is not clearly known. The purpose of present study was to examine the involvement of mu- and m-calpain in NMDA-induced excitotoxicity in the adult rat retina. Increased immunoreactivity of mu-calpain was noted in RGC layer cells and in the inner nuclear layer with maximal expression at 12 h after NMDA injection. This was further confirmed with Western blotting. TdT-mediated biotin-dUTP nick end labeling (TUNEL) positive cells in the inner retina co-localized with moderate or intense mu-calpain immunoreactivity. In contrast, there was no remarkable change in m-calpain immunoreactivity at any time point after NMDA injection. Simultaneous injection of 2 nmol of a calpain inhibitor (calpain inhibitor II) significantly reduced the number of TUNEL-positive cells in the inner retina at 18 h after NMDA injection and preserved RGC-like cells counted at 7 days after injection. The results of this study showed that p-calpain may be involved in mediating NMDA-induced excitotoxicity in the rat retina and calpain inhibitors may play a therapeutic role in NMDA related disease. (c) 2005 Elsevier B.V. All rights reserved.