神经毒素影响parkin介导线粒体形态调控机制  

Effect of Neurotoxins on Parkin Mediated Mitochondrial Morphology Regulation

作　　者：张新玲[1] 穆成龙[1] 王红霞[1] 朱玉山[1] 

机构地区：[1]南开大学生命科学学院,天津300071

出　　处：《南开大学学报（自然科学版）》2017年第3期40-43,共4页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：国家973项目(2011CB910903)

摘　　要：MPP+和6-OHDA是两种广泛用于构建帕金森疾病动物和细胞实验模型的神经毒素.许多研究表明:parkin蛋白功能异常是帕金森疾病发生的主要原因.前期研究发现,MPP+和6-OHDA处理SH-SY5Y神经细胞能诱导线粒体破碎,并且parkin蛋白表达下降,然而线粒体破碎是否与parkin减少有关,目前还不是很清楚.本研究发现MPP+和6-OHDA均能引起parkin的底物蛋白Drp1水平增加,而Drp1参与调控线粒体的分裂,线粒体分裂过度会破碎成点状.在parkin敲除的成纤维细胞内也发现线粒体破碎的现象,外源表达parkin质粒可以恢复线粒体的形态,从而证实MPP+和6-OHDA诱导线粒体破碎与parkin/Drp1有关.MPP~＋ and 6-OHDA are two neurotoxins widely used to Parkinson＇s animal model. Many studies found that mutation of parkin mainly cause Parkinson. Our experiments found that parkin protein level was downregulated and mitochondrial broken in SH-SY5 Y cells treated with MPP~＋ or 6-OHDA.However, it is not clear that broken of mitochondrial is related to the downregulation of parkin. The study identify that Drp1, one substrate of parkin, could be upregulated by MPP~＋ or 6-OHDA treatment, and then promoted mitochondrial fission. We also found that mitochondrial broken in parkin ko MEF cells and could be restored by expressing parkin plasmid tagged GFP. All results confirm that mitochondrial broken by MPP~＋ or 6-OHDA treatment is related to parkin/Drp1.

关 键 词：帕金森综合征 线粒体 PARKIN Drp1 

分 类 号：Q23[生物学—细胞生物学]