TRPC3参与α-突触核蛋白引起的线粒体损伤

doi:10.3969/j.issn.1006-7795.2017.06.016

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (6): 857-862.doi: 10.3969/j.issn.1006-7795.2017.06.016

• Alpha-突触核蛋白的致病机制 • 上一篇下一篇

TRPC3参与α-突触核蛋白引起的线粒体损伤

卢勇泉, 陈敏, 高歌, 段春礼, 鲁玲玲, 杨慧

首都医科大学基础医学院神经生物学系, 北京脑重大疾病研究院帕金森病研究所, 教育部神经变性病重点实验室, 北京 100069

收稿日期:2017-10-23 出版日期:2017-11-21 发布日期:2017-12-16
通讯作者: 杨慧 E-mail:huiyang@ccmu.edu.cn
基金资助:
国家重点研究发展计划（2016YFC1306002），国家自然科学基金（81371398，81371200），北京市自然科学基金（7131001），北京市创新团队建设提升计划（IDHT20140514），北京市教育委员会科技发展计划一般项目（KM201710025001）。

TRPC3 participates in α-synuclein-induced mitochondrial damage

Lu Yongquan, Chen Min, Gao Ge, Duan Chunli, Lu Lingling, Yang Hui

Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Center for Parkinson's Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing 100069, China

Received:2017-10-23 Online:2017-11-21 Published:2017-12-16
Supported by:
This study was supported by National Key Research and Development Plan of China (2016YFC1306002), National Natural Science Foundation of China (81371398, 81371200), Natural Science Foundation of Beijing (7131001), Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges Under Beijing Municipality (IDHT20140514), Scientific Research Common Program of Beijing Municipal Commission of Education (KM201710025001).

摘要/Abstract

摘要： 目的探讨经典型瞬时受体电位通道3（transient receptor potential canonical channel 3，TRPC3）是否参与α-突触核蛋白（α-synuclein，α-syn）引起的线粒体损伤。方法在α-syn过表达原代培养神经元、α-syn转基因及敲除小鼠模型，利用免疫印迹和免疫荧光技术检测TRPC3和α-syn在线粒体内的定位和表达；在原代培养神经元，运用MTT和乳酸脱氢酶法检测细胞活力和受损情况，JC-1法检测线粒体膜电势，观察敲减TRPC3对α-syn过表达引起的线粒体损伤和细胞损伤的影响。结果 TRPC3和α-syn共同表达于线粒体，过表达α-syn增加TRPC3在线粒体的分布，敲除α-syn则下调TRPC3在线粒体的分布。敲减TRPC3明显减轻过表达α-syn引起的线粒体膜电势下降和细胞毒性。结论 TRPC3可能参与过表达α-syn引起的线粒体损伤。

关键词: 帕金森病, 神经元, α-突触核蛋白, 瞬时受体电位通道3, 线粒体

Abstract: Objective To investigate the role of transient receptor potential canonical channel 3 (TRPC3)in the mitochondrial damage induced by aberrant α-synuclein (α-syn) accumulation.Methods Expressions of TRPC3 and α-syn in mitochondria were detected by Western blotting and immunofluorescence in α-syn-overexpressing primary neurons and α-syn transgenic and knock-out mice.The detection of mitochondrial membrane potential(MMP) by JC-1 showed mitochondrial damage and the detection of cell viability used MTT and lactated dehydrogenase(LDH) release assays in α-syn-overexpression primary neurons which TRPC3 was knocked down.Results TRPC3 and α-syn co-expressed in mitochondria. Neurons overexpressing α-syn increased mitochondrial TRPC3 expression and decreased MMP and cell viability. Suppressing TRPC3 expression partially reversed the α-syn-induced reductions in MMP and cell viability.Conclusion Mitochondrial TRPC3 may participate in α-syn-induced mitochondrial damage.

Key words: Parkinson's disease, neuron, α-synuclein, transient receptor potential canonical channel 3(TRPC3), mitochondria

中图分类号:

Q189

卢勇泉, 陈敏, 高歌, 段春礼, 鲁玲玲, 杨慧. TRPC3参与α-突触核蛋白引起的线粒体损伤[J]. 首都医科大学学报, 2017, 38(6): 857-862.

Lu Yongquan, Chen Min, Gao Ge, Duan Chunli, Lu Lingling, Yang Hui. TRPC3 participates in α-synuclein-induced mitochondrial damage[J]. Journal of Capital Medical University, 2017, 38(6): 857-862.

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TRPC3参与α-突触核蛋白引起的线粒体损伤

TRPC3 participates in α-synuclein-induced mitochondrial damage

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