Role of aldehyde dehydrogenase 2 in 1-methy-4-phenylpyridinium ion-induced aldehyde stress and cytotoxicity in PC12 cells

Neurochem Res. 2014 Sep;39(9):1767-75. doi: 10.1007/s11064-014-1376-1. Epub 2014 Jul 9.

Abstract

Aldehyde stress contributes to molecular mechanisms of cell death and the pathogenesis of Parkinson's disease (PD). The neurotoxin 1-Methy-4-Phenylpyridinium Ion (MPP(+)) is commonly used to model PD. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme detoxifying aldehydes. The aim of this study is to evaluate whether MPP(+)-induced neurotoxicity is involved in aldehyde stress by modulation of ALDH2. Our results demonstrated that treatment of PC12 cells with MPP(+) leads to aldehyde stress by increasing in loads of malondialdehyde and 4-hydroxynonenal, which indicated that MPP(+)-induced aldehyde stress contributes to its cytotoxicity in PC12 cells. We also showed that MPP(+) up-regulates the expression and activity of ALDH2 in PC12 cells and that inhibition of ALDH2 by its specific inhibitor daidzin prevents MPP(+)-induced decrease in cell viability and increases in apoptosis, oxidative stress and aldehyde stress in PC12 cells. These findings suggest that aldehyde stress contributes to MPP(+)-induced toxicity in PC12 cells by upregulation of ALDH2. This study provides a novel insight into the role of ALDH2 in the neurotoxicity of MPP(+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Aldehyde Dehydrogenase / antagonists & inhibitors
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Aldehydes / toxicity*
  • Animals
  • Enzyme Inhibitors / pharmacology
  • Isoflavones / pharmacology
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / metabolism*
  • Oxidative Stress / drug effects*
  • PC12 Cells
  • Rats

Substances

  • Aldehydes
  • Enzyme Inhibitors
  • Isoflavones
  • Mitochondrial Proteins
  • daidzin
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • Aldh2 protein, rat
  • 1-Methyl-4-phenylpyridinium