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Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells.
- Source :
-
Neurotoxicity research [Neurotox Res] 2010 May; Vol. 17 (4), pp. 332-43. Date of Electronic Publication: 2009 Sep 10. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- 1-Methyl-4-phenylpyridinium metabolism
Adenosine Triphosphate metabolism
Analysis of Variance
Cell Differentiation drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Gene Expression Regulation, Neoplastic drug effects
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Humans
Ion Channels genetics
Membrane Potential, Mitochondrial drug effects
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
MicroRNAs pharmacology
Mitochondrial Proteins genetics
Mitochondrial Uncoupling Proteins
Neuroblastoma pathology
Reactive Oxygen Species metabolism
Uncoupling Protein 2
1-Methyl-4-phenylpyridinium toxicity
Herbicides toxicity
Ion Channels physiology
Leptin pharmacology
Mitochondrial Proteins physiology
Neuroprotective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-3524
- Volume :
- 17
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurotoxicity research
- Publication Type :
- Academic Journal
- Accession number :
- 19763737
- Full Text :
- https://doi.org/10.1007/s12640-009-9109-y