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The Involvement of Heat Shock Protein in the Delayed Neuronal Death of the Mongolian Gerbil Hippocampal Pyramidal Neurons.

热休克蛋白参与蒙古沙鼠海马锥体神经元延迟性神经元死亡。

基本信息

批准号：
15591666
负责人：
TSUCHIDA Hideaki
金额：
$ 1.79万
依托单位：
KANAZAWA MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591666/
关键词：
Mongolian Gerbil Hippocampus Apoptosis Heat Shock Protein 90 熱ショックタンパク90

项目摘要

Although apoptosis is most likely the main cause of delayed neuronal death (DND) in the hippocampal pyramidal neurons after transient ischemia, the molecular mechanisms underlying this phenomenon have not been elucidated clearly. Recently Heat Shock Protein 90 (HSP90) attracts attention as one of protective factor for stress, but the details of its function are scarsely elucidated.Male Mongolian gerbils (n=), weighing 60 to 70 g, were anesthetized with isoflurane. Transient forebrain ischemia was induced by occluding the bilateral common carotid arteries for 5 minutes. A sham-operation group was not subjected to ischemia and served as the negative control. The animals were sacrificed 6-120 hours after ischemia and the hippocampi were dissected. We analyzed expression and localization of HSP90 using RT-PCR, Western blot analysis, and immunohistochemistry. In addition, HSP90 was induced by geranylgeranyl acetone and the function of HSP90 was examined.RT-PCR and Western blot analysis showed that HSP90 mRNA was up-regulated at 6 to 48 hours and HSP90 was increased at 12 to 48 hours after ischemia in the pyramidal neurons. While an increase in HSP90 was also verified by immunohistochemistry in the hippocampus after ischemia, the expression was weak in the CAI region compared to that in CA2. Intraperitoneal administration of geranylgeranylacetone, 400 mg/kg, 4 hours before ischemia induced expression of HSP90 at 48 hours after ischemia and ameliorated DNA fragmentation and DND at 96 hours after ischemia in the pyramidal neurons.These results strongly indicate that HSP90 is protective against DND after transient ischemia in the Mongolian Gerbil. In addition, difference in the ability of HSP90 induction may be involved in selective neuronal vulnerability.

虽然细胞凋亡是短暂缺血后海马锥体神经元迟发性神经元死亡（delayed neuronal death，DND）的主要原因，但其分子机制尚不清楚。热休克蛋白90（Heat Shock Protein 90，HSP 90）是近年来引起人们注意的应激保护因子之一，但其具体功能尚不清楚。通过阻断双侧颈总动脉5分钟诱导短暂性前脑缺血。假手术组不进行缺血处理，作为阴性对照。在缺血后6-120小时处死动物，解剖海马。采用RT-PCR、Western blot和免疫组织化学方法分析HSP 90的表达和定位。RT-PCR和Western blot分析显示，缺血后6 ~ 48 h锥体神经元HSP 90 mRNA表达上调，12 ~ 48 h锥体神经元HSP 90表达增加。虽然增加HSP 90也证实了免疫组织化学在缺血后的海马，在CAI区的表达较弱，在CA 2。缺血前4 h腹腔注射香叶基香叶基丙酮（400 mg/kg）可诱导缺血后48 h海马锥体神经元表达HSP 90，并减轻缺血后96 h海马锥体神经元DNA断裂和DND，提示HSP 90对沙土鼠短暂缺血后DND具有保护作用。此外，HSP 90诱导能力的差异可能与选择性神经元易损性有关。