Ischemic preconditioning induces chaperone hsp70 expression and inhibits protein aggregation in the CA1 neurons of rats

作     者：葛鹏飞 罗天飞 张纪周 陈大伟 栾永新 付双林 Peng-Fei GE;Tian-Fei LUO;Ji-Zhou ZHANG;Da-Wei CHEN;Yong-Xin LUAN;Shuang-Lin FU

作者机构：吉林大学附属第一医院神经外科长春130021 吉林大学白求恩医学院生物化学系长春130021 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2008年第24卷第5期

页      面：288-296页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：the grants from the Department of Science and Technology of Jilin Province, China (No. 20070721) the Bureau of Science and Technology of Changchun, Jilin Province, China (No. 2007129) 

主　　题：ischemic preconditioning protein aggregation chaperone hsp70 

摘      要：Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10- min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Results Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region （P 〈 0.01 vs 10-min ischemia group）. Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates（P〈0.01 vs 10-min ischemia group）.Conelusion Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.