Apelin-36 exerts the cytoprotective effect against MPP+-induced cytotoxicity in SH-SY5Y cells through PI3K/Akt/mTOR autophagy pathway

Abstract

AimsParkinson's disease (PD) is a common neurodegenerative disease typically associated with the accumulation of α-synuclein. Autophagy impairment is thought to be involved in the dopaminergic neurodegeneration in PD. We investigate the effect of Apelin-36 on the activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/the mammalian target of rapamycin (mTOR) autophagy pathway in 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells, which is involved in the cytoprotective effect of Apelin-36. Main methodsSH-SY5Y cells were treated with 1-Methyl-4-phenylpyridine (MPP+) with or without Apelin-36. The cell viability, apoptotic ratio, the form of autophagic vacuoles, the expression of tyrosine hydroxylase (TH), α-synuclein, phosphorylation of PI3K, AKT, mTOR, microtubule-associated protein 1 Light Chain 3 II/I (LC3II/I) and p62 were detected to investigate the neuroprotective effect of Apelin-36. Key findingsThe results indicate that Apelin-36 significantly improved the cell viability and decreased the apoptosis in MPP+-treated SH-SY5Y cells. The decreased expression of tyrosine hydroxylase (TH) induced by MPP+ was significantly increased by Apelin36 pretreatment. Moreover, Apelin36 significantly increased the autophagic vacuoles. The ratio of LC3II/I was significantly increased by Apelin36, as well as the decreased p62 expression. In addition, the activated PI3K/AKT/mTOR pathway induced by MPP+ was significantly inhibited by Apelin36. Additionally, Apelin36 significantly decreased the α-synuclein expression. Furthermore, the cytoprotective effect of Apelin-36 was weakened by pretreatment with Insulin-like Growth Factor-1 (IGF-1), an activator of PI3K/Akt, and MHY1485, an mTOR activator. SignificanceOur results demonstrated that Apelin-36 protects against MPP+-induced cytotoxicity through PI3K/Akt/mTOR autophagy pathway in PD model in vitro, which provides a new theoretical basis for the treatment of PD.