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，人们认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，是分子伴侣的成员之一，在正常蛋白质合成的后期发挥作用。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hsp 60和hsp 10基因诱导的解剖学和时间模式。1)局灶性脑缺血。采用Sprague-Dawley大鼠大脑中动脉闭塞模型，通过原位杂交技术和RTPCR检测hsp60和hsp10 mRNA的分布。暂时 MCA 闭塞 30 分钟后，两种 mRNA 在唯一缺血的皮质中被诱导，直到再循环 24 小时。在90分钟的闭塞中，两种mRNA在MCA区域的周围被诱导，并且也在远离缺血区域的同侧海马中被诱导。再循环8小时时诱导达到最大。2)前脑缺血。通过低血压和双侧颈动脉闭塞相结合产生缺血模型。两种 mRNA 首先在齿状回中被诱导，然后在海马、壳核和大脑皮层的 CA1-4 中被诱导。缺血10分钟后24小时，除CA1区外，两种mRNA的诱导均恢复至对照水平。然而，再循环 4 天后，CA1 中两种 mRNA 的表达均消失，这与延迟性神经元死亡的发生一致。这项研究清楚地证明了大鼠局灶性或前脑缺血后 hsp60 和 hsp10 mRNA 的解剖学和时间顺序模式。第一次。由于 hsp60 和 hsp10 的诱导模式完全一致，伴侣蛋白似乎参与了缺血条件下蛋白质合成的修复。