Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating heme oxygenase-1 expression

J Neurol Sci. 2014 Aug 15;343(1-2):115-9. doi: 10.1016/j.jns.2014.05.051. Epub 2014 Jun 2.

Abstract

Oxidative stress is involved in the pathogenesis of Parkinson's disease (PD). Edaravone has been shown to have a neuroprotective effect. In the present work, we investigated the effect of edaravone on 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells. Edaravone inhibited the decrease of cell viability and apoptosis induced by MPP(+) in PC12 cells. In addition, edaravone alleviated intracellular reactive oxygen species (ROS) production. MPP(+) induced heme oxygenase-1 (HO-1) expression, which was further enhanced by edaravone. The inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of edaravone. So edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating HO-1 expression. The data showed that edaravone was neuroprotective and could be potentially therapeutics for PD in future.

Keywords: 1-Methyl-4-phenylpyridinium; Edaravone; Heme oxygenase-1; Oxidative stress; PC12; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Analysis of Variance
  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Edaravone
  • Enzyme Inhibitors
  • Flow Cytometry
  • Free Radical Scavengers / pharmacology*
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Neurotoxins / pharmacology*
  • Oxidative Stress / drug effects*
  • PC12 Cells / drug effects
  • Protoporphyrins / pharmacology
  • Rats
  • Up-Regulation / drug effects*

Substances

  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Neurotoxins
  • Protoporphyrins
  • zinc protoporphyrin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Edaravone
  • Antipyrine