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

近年来，人们认识到分子伴侣与蛋白质折叠有关。伴侣蛋白由HSP60和HSP10两个亚基组成，是分子伴侣中的一员，在正常蛋白质合成的后期发挥作用。然而，伴侣在包括缺血损伤在内的应激条件下的作用还没有完全被了解。在这项研究中，我们研究了局灶性脑缺血后热休克蛋白60和热休克蛋白10基因诱导的解剖学和年代学模式。采用SD大鼠大脑中动脉闭塞模型，用原位杂交技术和RT-PCR方法检测HSP60和HSP10mRNA的表达。大脑中动脉暂时阻断30min后，两种mRNAs均在唯一的缺血区皮质中表达，直至再灌流24 h。结扎90min后，两种mRNAs均在大脑中动脉周围和远离缺血区的同侧海马区均有表达。2)前脑缺血再灌流8h时诱导作用最强。采用低血压和双侧颈总动脉结扎相结合的方法制作大鼠脑缺血模型。这两种mRNAs首先在齿状回表达，然后在海马区、壳核和大脑皮层的CA1-4区诱导。缺血10min后24小时，除CA1区外，两种基因的表达均恢复到对照水平。然而，这两种mRNAs在CA1区的表达在再循环4天后消失，这与迟发性神经元死亡的发生一致。本研究首次清楚地展示了大鼠局灶性脑缺血或前脑缺血后HSP60和HSP10mRNAs的解剖和时间模式。由于HSP60和HSP10的诱导模式完全一致，分子伴侣似乎参与了缺血条件下蛋白质合成的修复。

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.