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，已经意识到分子伴侣与蛋白质折叠有关。伴侣蛋白由两个亚基Hsp60和Hsp10组成，这是分子伴侣作用的成员，在正常蛋白质系统的后期。但是，伴侣蛋白在包括缺血性损伤在内的应力条件下的作用尚未完全理解。在这项研究中，我们研究了脑缺血后HSP 60和HSP 10基因诱导的解剖学和年代学模式。1）局灶性脑缺血。使用Sprague-Dawley大鼠中脑动脉闭塞模型，通过原位杂交技术和RTPCR检查了Hsp60和Hsp10 mRNA的分布。临时MCA闭塞30分钟后，直到再循环24小时，在唯一的缺血皮层中诱导了这两个mRNA。在90分钟的闭塞中，在MCA领域的外围诱导了两个mRNA，并在远离缺血区域的同侧海马中诱导。诱导在再循环8小时时最大。2）前脑缺血。缺血模型是通过低血压和双侧颈动脉阻塞的组合产生的。首先在齿状回中诱导两个mRNA，然后在海马，梭子和脑皮质的CA1-4中诱导。缺血10分钟后24小时，两个mRNA的诱导恢复到控制水平，除了CA1部门。然而，在再循环4天后与延迟神经元死亡的发生后，两种mRNA在CA1中的表达消失了。这项研究清楚地证明了HSP60和HSP10 mRNA在大鼠中首次局灶性或前脑缺血后HSP60和HSP10 mRNA的解剖学和年代学模式。由于HSP60和HSP10的诱导模式完全一致，因此伴侣蛋白似乎与缺血条件下的蛋白质体式有关。