Mild MPP+ exposure-induced glucose starvation enhances autophagosome synthesis and impairs its degradation

Sci Rep. 2017 Apr 26:7:46668. doi: 10.1038/srep46668.

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, mainly characterised by the progressive loss of dopaminergic neurons. MPP+ has been widely used as a PD-related neurotoxin, and their reports suggested the several hypotheses for neuronal cell death. However, most of these hypotheses come from the studies about the acute MPP+ exposure. We previously revealed that mild MPP+ exposure (10 and 200 μM), which induces gradual cell death, impairs autophagosome degradation at 48 h. In the present study, we further investigated the specific events of mild MPP+ exposure and revealed that mild MPP+ exposure causes the cell death through glucose starvation, but not acute toxic model (2.5 and 5 mM). At 36 h after mild MPP+ exposure, autophagosome synthesis was enhanced owing to glucose starvation and continued to enhance until 48 h, despite impaired autophagosome degradation. Inhibition of autophagosome synthesis reduced mild MPP+-induced cell death. In conclusion, we clarified that glucose starvation-enhanced autophagosome synthesis occurs at an earlier stage than impaired autophagosome degradation and is important in mild MPP+ toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology*
  • Autophagosomes / drug effects*
  • Autophagosomes / metabolism
  • Autophagy / drug effects*
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Glucose / metabolism*
  • Herbicides / pharmacology
  • Humans
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • RNA Interference

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Herbicides
  • Glucose
  • 1-Methyl-4-phenylpyridinium