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

Life Sci. 2019 May 1:224:95-108. doi: 10.1016/j.lfs.2019.03.047. Epub 2019 Mar 21.

Abstract

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.

Keywords: 1-Methyl-4-phenylpyridine; Apelin-36; Apoptosis; Autophagy; Parkinson's disease.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / adverse effects*
  • Apelin / genetics
  • Apelin / metabolism*
  • Apoptosis
  • Autophagy
  • Humans
  • Neuroblastoma / chemically induced
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neuroblastoma / prevention & control*
  • Neuroprotective Agents / pharmacology*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Cells, Cultured

Substances

  • APLN protein, human
  • Apelin
  • Neuroprotective Agents
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinase
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • 1-Methyl-4-phenylpyridinium