Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage

作     者：Jiaxiang Shao Xiao Yang Tengyuan Liu Tingting Zhang Qian Reuben Xie Weiliang Xia 

作者机构：State Key Laboratory of Oncogenes and Related Genes Renji-Med X Stem Cell Research Center Ren Ji Hospital School ofBiomedical Engineering Shanghai Jiao Tong University Shanghai 200030 China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2016年第7卷第4期

页      面：281-290页

核心收录：

学科分类：071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 090102[农学-作物遗传育种] 0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 0901[农学-作物学] 0836[工学-生物工程] 

主　　题：SIRT6 oxidative stress neuronal damage,autophagy AKT 

摘      要：SIRT6 is a NAD＊-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation （OGD） has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species （ROS） production under oxidative stress. Mechanistic study revealed that SlRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued HzO2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stressinduced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.