Capsazepine抑制培养海马神经元网络线粒体转运(英文)  

Capsazepine inhibits mitochondrial transport in cultured hippocampal neuronal networks of rat

作　　者：付敏[1] 潘丽洁[1] 孙朝晖[1] 左焕琮[1] 谢佐平[2] 

机构地区：[1]清华大学医学院,北京100084 [2]清华大学生物科学与生物技术学系,细胞膜与膜生物工程国家重点实验室,北京100084

出　　处：《神经解剖学杂志》2009年第3期239-243,共5页Chinese Journal of Neuroanatomy

基　　金：清华裕元医学基金(20240000513);国家重点基础研究发展规划(973项目,2005CB522503)资助项目

摘　　要：capsazepine(CZP)是辣椒素的合成类似物,也是野香草型瞬时感受器电位通道1(TRPV1)的选择性抑制剂。TRPV1在体内有广泛的表达谱,使CZP有广泛的作用位点。除此之外,以往的研究结果表明CZP除了作用于TRPV1外还有更复杂的信号通路。本课题研究了CZP对体外培养的大鼠海马神经元网络内线粒体转运的作用并分析其可能机制。结果显示:20μmol/L的CZP可有效抑制原代培养海马神经元网络中的线粒体转运。CZP急性作用不引起胞内钙离子浓度的升高,也不引起细胞的调亡。胞外更换为无外钙记录液,或者将GSK3β抑制剂SB415286与CZP共孵育,均不影响CZP对线粒体转运的抑制作用。然而,将BAPTA-AM与CZP共孵育,抑制了CZP对线粒体转运的抑制作用。本研究结果表明,CZP直接通过胞内钙信号通路影响神经元的线粒体转运,与胞外钙流或转运蛋白的磷酸化无关。Capsazepine is a synthetic analogue of eapsaicin and a selective inhibitor of transient receptor potential vanilloid 1 channel （TRPV1）. TRPVI has wide expression profile, providing extensive targets for capsazepine. Evidence from previous studies showed that capsazepine acted more complex effects through other than TRPV1 signal pathway. In this study, we examined its effect and underlying mechanisms on mitoehondrial transport of cultured hippocampal neurons in rats. The data showed that the number of the moving mitochondria in primarily cultured hippocampal neurons was remarkably decreased by 20 μmol/L capsazepine. Contradicted to previous study, the intracellular calcium concentration was not elevated. Capsazepine did not induce cell death in acute incubation. The inhibitory effect of capsazepine was not prevented by co-application of SB415286, the inhibitor of GSK313 or by replacing extracellular recording solution to calcium-free saline, but prevented by co-application of BAPTA-AM. These results indicated that eapsazepine inhibited mitochondrial transport in hippocampal neurons through intracellular calcium signal pathways, with no involvement of extracellular calcium influx or transport protein phosphorylation.

关 键 词：CAPSAZEPINE TRPV1激动剂 线粒体转运 胞内钙 海马 大鼠 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]