Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells.

Philip Wing Lok Ho, Hui Fang Liu, Jessica Wing Man Ho, Wei Yi Zhang, Andrew Chi Yuen Chu, Ken Hon Hung Kwok, Xuan Ge, Koon Ho Chan, David Boyer Ramsden, Shu Leong Ho

Research output: Journal article publicationJournal articleAcademic researchpeer-review

49 Citations (Scopus)


Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity.

Original languageEnglish
Pages (from-to)332-343
Number of pages12
JournalNeurotoxicity Research
Issue number4
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • General Neuroscience
  • Toxicology


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