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The expiession and function of molecular chaperone in the central nervous system.

中枢神经系统分子伴侣的表达和功能。

基本信息

批准号：
10671281
负责人：
KINOUCHI Hiroyuki
金额：
$ 1.98万
依托单位：
AKITA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671281/
关键词：
heat shock protein hsp10 hsp60 chaperonin cerebral ischemia Molecular chaperone Stress protein HSP60 HSP10

项目摘要

Recently, it has been realized that molecular chaperone is implicated in the protein folding. Chaperonin being composed of two subunits, HSP60 and HSP10 that is one the member of molecular chaperones act in the late stage of the normal protein systhesis. However, the role of chaperonin under the stress condition including ischemic insults has not been fully understood yet. In this study, we investigated the anatomical and chronological patterns for the induction of hsp 60 and hsp 10 genes after cerebral ischemia.1) Focal cerebral ischemia. Using middle cerebral artery occlusion model in Sprague-Dawley rats, the distribution of hsp60 and hsp10 mRNA was examined by in situ hybridization technique and RTPCR. After 30 min of temporary MCA occlusion, both mRNAs were induced in the only ischemic cortex until 24 h of recirculation. In 90 min occlusion, both mRNAs were induced in the periphery of the MCA territory and were also induced in the ipsilateral hippocampus that is distant from the ischemic regions. The induction was maximal at 8 h of recirculation.2) Forebrain ischemia. The ischemic model was produced by the combination of hypotension and bilateral carotid artery occlusion. Both mRNAs were induced in the dentate gyrus first and then in the CA1-4 of hippocampus, putamen, and cerebral cortex. 24 h after 10 min of ischemia, the induction of both mRNAs returned to the control level except in the CA1 sector. However, the expression of both mRNAs in the CA1 disappeared after 4 days of recirculation consistent with the occurrence of the delayed neuronal death.This study clearly demonstrated the anatomical and chronological pattern of both hsp60 and hsp10 mRNAs following either focal or forebrain ischemia in rat for the first time. Since the induction pattern of hsp60 and hsp10 are completely consistent, chaperonin seems to be implicated in the repair of the protein systhesis under the ischemic conditions.

最近，人们已经意识到分子伴侣参与蛋白质折叠。分子伴侣蛋白由HSP 60和HSP 10两个亚基组成，是分子伴侣的成员之一，在正常蛋白质合成的后期起作用。然而，伴侣蛋白在包括缺血性损伤在内的应激条件下的作用尚未完全了解。在这项研究中，我们研究了脑缺血后热休克蛋白60和热休克蛋白10基因诱导的解剖和时间模式。1）局灶性脑缺血。采用SD大鼠大脑中动脉闭塞模型，应用原位杂交技术和RT-PCR技术检测hsp 60和hsp 10 mRNA在脑内的分布。30分钟的临时MCA闭塞后，这两种mRNA诱导的唯一缺血皮质，直到24小时的再循环。在90分钟的闭塞，这两种mRNA的诱导在周边的MCA领土，也诱导在同侧海马是远离缺血区域。再循环8 h时诱导作用最强。2）前脑缺血。采用低血压和双侧颈总动脉阻断相结合的方法建立脑缺血模型。两种mRNA首先在齿状回中诱导，然后在海马、壳核和大脑皮层的CA 1 -4中诱导。缺血10 min后24 h，除CA 1区外，两种mRNA的表达均恢复到对照组水平。然而，这两种mRNA的表达在再循环4天后消失，与迟发性神经元死亡的发生相一致。本研究清楚地表明，无论是局灶性或前脑缺血后大鼠海马CA 1区hsp 60和hsp 10 mRNA的解剖和时间模式。由于热休克蛋白60和热休克蛋白10的诱导模式是完全一致的，伴侣蛋白似乎涉及在缺血条件下的蛋白质合成的修复。