GAPDH降解途径在鱼藤酮诱导多巴胺能神经元损伤中的作用  

The role of GAPDH degradation pathway in rotenone-induced dopaminergic cell injury

作　　者：陈春暖[1] 陈祥荣[2] 蔡乾昆[1] 叶励超[1] 蔡若蔚[1] 万琼红[1] 王涛[3] Chen Chunnuan;Chen Xiangrong;Cai Qiankun;Ye Lichao;Cai Ruowei;Wan Qionghong;Wang Tao(Department of Neurology;Department of Neurosurgery,Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,China;Department of Neurology,Affiliated Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430020,China)

机构地区：[1]福建医科大学附属第二医院神经内科,泉州362000 [2]福建医科大学附属第二医院神经外科,泉州362000 [3]华中科技大学同济医学院附属协和医院神经内科,武汉430020

出　　处：《中国组织化学与细胞化学杂志》2018年第4期321-326,共6页Chinese Journal of Histochemistry and Cytochemistry

基　　金：福建省自然科学基金青年创新项目(2015J05148);福建省卫生计生委青年科研课题(2014-1-67);泉州市科技局科技计划重点项目(2014Z45)

摘　　要：目的探讨GAPDH降解途径在鱼藤酮(rotenone)诱导的多巴胺能神经元损伤中的作用。方法用鱼藤酮诱导多巴胺能神经细胞SH-SY5Y建立帕金森病(Parkinson’s disease,PD)细胞模型,并分别加入蛋白酶体和自噬抑制剂和激活剂,显微镜观察细胞形态,MTT法检测细胞活性,Western blot检测GAPDH的表达及降解。结果鱼藤酮、蛋白酶体和自噬途径抑制剂可导致细胞活性下降,各药物组细胞生长受抑制;在鱼藤酮诱导的SH-SY5Y细胞内GAPDH水平上调,加入蛋白酶体和自噬途径抑制剂能够进一步上调GAPDH水平,而加入两个降解途径的激活剂则显著抑制鱼藤酮对GAPDH水平的上调作用。结论蛋白酶体和自噬溶酶体途径功能异常在GAPDH代谢中发挥重要作用,两者均参与GAPDH的降解。激活这两条降解途径可增加过表达的GAPDH的清除,可能成为PD治疗潜在的新靶点。Objective To investigate the role of GAPDH degradation pathway in rotenone-induced dopaminergic cell injury. Methods Parkinson＇s disease （PD） cell model was established through inducing SH-SYSY dopaminergic neuron-like cells by rotenone. Cells were then treated with inhibitors or activators ofproteasome and autophagy pathways. Cell morphology under light microscopy was recorded and viability was measured by MTT assay. The protein expression and degradation of GAPDH was detected by Western blot. Results Both rotenone treatment and the inhibition of proteasome and autophagy pathways lead to decreased cell viability and cell growth inhibition. GAPDH level was up-regulated by rotenone treatment as well as by the inhibition of proteasome and autophagy pathways, while it was down-regulated in response to the activation of the two protein degradation pathways. Conclusion Both proteasome and autophagy pathways are involved in the metabolism of GAPDH. Activation of the two pathways increases the clearance of GAPDH and provides a potential therapeutic strategy for Parkinson＇s disease.

关 键 词：帕金森病 鱼藤酮 3-磷酸甘油醛脱氢酶 泛素-蛋白酶体系统 自噬-溶酶体途径 

分 类 号：R34[医药卫生—基础医学]