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

Aims: Parkinson'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 methods: SH-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 findings: The 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.

Significance: Our 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.