Open AccessSIRT3 Protects Rotenone-induced Injury in SH-SY5Y Cells by Promoting Autophagy through the LKB1-AMPK-mTOR Pathway
Author(s) -
Meng Zhang,
Yongning Deng,
Jingyi Zhang,
Jie Liu,
Yanbo Li,
Hua Su,
Qing Qu
Publication year - 2018
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2017.0517
Subject(s) - autophagy , sirt3 , ampk , pi3k/akt/mtor pathway , neuroprotection , microbiology and biotechnology , viability assay , rotenone , chemistry , phosphorylation , sirtuin , cancer research , biology , apoptosis , signal transduction , protein kinase a , mitochondrion , pharmacology , acetylation , biochemistry , gene
SIRT3 is a class III histone deacetylase that modulates energy metabolism, genomic stability and stress resistance. It has been implicated as a potential therapeutic target in a variety of neurodegenerative diseases, including Parkinson's disease (PD). Our previous study demonstrates that SIRT3 had a neuroprotective effect on a rotenone-induced PD cell model, however, the exact mechanism is unknown. In this study, we investigated the underlying mechanism. We established a SIRT3 stable overexpression cell line using lentivirus infection in SH-SY5Y cells. Then, a PD cell model was established using rotenone. Our data demonstrate that overexpression of SIRT3 increased the level of the autophagy markers LC3 II and Beclin 1. After addition of the autophagy inhibitor 3-MA, the protective effect of SIRT3 diminished: the cell viability decreased, while the apoptosis rate increased; α-synuclein accumulation enhanced; ROS production increased; antioxidants levels, including SOD and GSH, decreased; and MMP collapsed. These results reveal that SIRT3 has neuroprotective effects on a PD cell model by up-regulating autophagy. Furthermore, SIRT3 overexpression also promoted LKB1 phosphorylation, followed by activation of AMPK and decreased phosphorylation of mTOR. These results suggest that the LKB1-AMPK-mTOR pathway has a role in induction of autophagy. Together, our findings indicate a novel mechanism by which SIRT3 protects a rotenone-induced PD cell model through the regulation of autophagy, which, in part, is mediated by activation of the LKB1-AMPK-mTOR pathway.