VPS35WT逆转LRRK2G2019S所致的非神经细胞的tau蛋白过度磷酸化及相关功能缺陷  

VPS35WT Can Reverse Tau Phosphrylation and the Disfunctions Caused by Overexpression of LRRK2G2019S in Non-neronal Cells

作　　者：王纬 王杰[1,2] 沈华超[1,2] 叶民[2] 丁新生[1] WANG Wei;WANG Jie;SHEN Hua-chao;YE Min;DING Xin-sheng(BenQ Institute of Neurology,BenQ Hospital Affiliated to Nanjing Medical University,Nanjing 210029,China;Department of Neurology,BenQ Hospital Affiliated to Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学明基神经病学研究所,南京210029 [2]南京医科大学附属明基医院神经内科,南京210029

出　　处：《中国临床神经科学》2019年第5期481-486,共6页Chinese Journal of Clinical Neurosciences

基　　金：南京市卫局医学科技发展项目(编号:YKK16243);南京医科大学科技发展基金面上项目(编号:2015NJMU171)

摘　　要：目的探究逆膜复合体亚基VPS35对富亮氨酸重复激酶2(LRRK2)G2019S所导致的tau蛋白功能缺陷的影响。方法采用HeLa细胞转染过表达LRRK2G2019S质粒(LRRK2G2019S组)、囊泡分选蛋白35(VPS35)WT质粒(VPS35WT组)、共转染VPS35WT+LRRK2G2019S(VPS35WT+LRRK2G2019S共转染组)和空载对照组(对照组)。采用Western blot法和免疫荧光组化法检测HeLa细胞内tau蛋白磷酸化水平、细胞骨架形态及在低剂量毒物作用下细胞死亡率的变化。结果VPS35WT+LRRK2G2019S共转染可以进一步逆转过表达LRRK2G2019S的HeLa细胞的tau蛋白磷酸化,稳定细胞骨架,提高细胞对毒物的抵抗力,降低细胞的死亡率(均P<0.01)。结论VPS35WT可以逆转LRRK2G2019S所致的HeLa细胞相关功能障碍。Aim To investigate the effects of vesicle protein sorting-35 ( VPS35) in tau dysfunction caused by leucine-rich repeat kinase 2( LRRK2) G2019S.Methods Western blot and immunofluorescence staining were adopted to compared the differences in Tau phosphrylation,structure changes and mortality after exposured to small doses of toxins between HeLa cells with overexpressed LRRK2G2019S and HeLa cells with coexpression of VPS35WT + LRRK2G2019S.Results Coexpression of VPS35WT could reverse the affected tau phosphorylation,stabilize cell structure,provide resistance to toxins and decrease mortality in HeLa cells with overexpressed LRRK2G2019S.Conclusion VPS35WT can reverse the dysfunctions caused by overexpression of LRRK2 G2019S in HeLa cells.

关 键 词：囊泡分选蛋白35 富亮氨酸重复激酶2 TAU蛋白磷酸化 HELA细胞 

分 类 号：R49.1[医药卫生—康复医学] R742[医药卫生—临床医学]