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

Philip Wing Lok Ho, David Yiu Leung Chan, Ken Hon Hung Kwok, Andrew Chi Yuen Chu, Jessica Wing Man Ho, Michelle Hiu Wai Kung, David Boyer Ramsden, Shu Leong Ho

Research output: Journal article publicationJournal articleAcademic researchpeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)261-268
Number of pages8
JournalJournal of Neuroscience Research
Volume81
Issue number2
DOIs
Publication statusPublished - 15 Jul 2005
Externally publishedYes

Keywords

  • Mitochondria
  • MPP
  • Neuroprotection
  • Oxidative stress
  • Uncoupling protein

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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