Ethyl pyruvate protects PC12 cells from dopamine-induced apoptosis

Eur J Pharmacol. 2005 Jan 31;508(1-3):57-68. doi: 10.1016/j.ejphar.2004.12.020. Epub 2005 Jan 7.

Abstract

Pyruvate acid can protect cells against oxidative damage. However, its instability limits its usefulness as a therapeutic agent. In this study, we examined the effect of ethyl pyruvate, an aliphatic ester derived from pyruvate acid, on dopamine-induced cytotoxicity in rat pheochromocytoma PC12 cells. The results demonstrated that dopamine induced apoptosis in PC12 cells accompanied with increases of intercellular reactive oxygen species, nuclear translocation of nuclear transcription factor kappa B (NF-kappaB) and expression of p53 and decrease of mitochondrial transmembrane potential. Ethyl pyruvate markedly reduced the dopamine-induced production of reactive oxygen species, nuclear translocation of NF-kappaB, upregulation of p53, loss of mitochondrial transmembrane potential and apoptosis in PC12 cells. The results suggested that ethyl pyruvate might protect PC12 cells against dopamine by suppressing intercellular oxidative stress and modulating key signal pathways of apoptosis, and that ethyl pyruvate might be used as a potential therapeutic agent for Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cell Survival / drug effects
  • Dopamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Hydrogen Peroxide / metabolism
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / physiology
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • NF-kappa B / metabolism
  • PC12 Cells
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyruvates / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • bcl-2-Associated X Protein

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Pyruvates
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • ethyl pyruvate
  • Hydrogen Peroxide
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Dopamine
  • Acetylcysteine