Methyl-4-phenylpyridinium ion modulates expression of mitochondrial uncoupling proteins 2, 4, and 5 in catecholaminergic (SK-N-SH) cells

J Neurosci Res. 2005 Jul 15;81(2):261-8. doi: 10.1002/jnr.20569.

Abstract

Methyl-4-phenylpyridinium ion (MPP(+)), a specific dopaminergic neurotoxin, inhibits mitochondrial complex I activity, generates reactive oxygen species (ROS), reduces ATP production, and induces cell death. We explored changes in expression of uncoupling proteins (UCPs 2, 4, and 5) following MPP(+)-induced toxicity in SK-N-SH cells over 72 hr at the transcriptional (quantification of mRNA by real-time RT-PCR) and translational (Western analysis) levels. UCP5 mRNA and protein were markedly up-regulated (1 mM MPP(+) at 72 hr caused a twofold increase, P < 0.01), as was UCP4 mRNA, albeit to a much lesser extent. Surprisingly, UCP2 mRNA levels decreased at 24 hr (P < 0.05) but thereafter significantly increased to greater than control levels at 72 hr (P < 0.05), although UCP2 protein levels were decreased throughout (1 mM MPP(+) at 72 hr caused a reduction of 50%, P < 0.01). The increase in ROS production may be attenuated by UCP4 and UCP5 up-regulation. The consequence of decreased UCP2 levels is unclear, although this may represent an adaptive response to declines in ATP levels, the subsequent increase in mRNA being a response to further increases in oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Cell Line, Tumor
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Ion Channels
  • Membrane Transport Proteins / drug effects*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / drug effects*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Uncoupling Proteins
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotoxins / toxicity*
  • RNA, Messenger / analysis
  • Uncoupling Protein 2

Substances

  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Mitochondrial Uncoupling Proteins
  • Nerve Tissue Proteins
  • Neurotoxins
  • RNA, Messenger
  • SLC25A14 protein, human
  • SLC25A27 protein, human
  • UCP2 protein, human
  • Uncoupling Protein 2
  • 1-Methyl-4-phenylpyridinium
  • Dopamine