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

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。

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.