期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2017.00164
关键词
Parkinson's disease; SH-SY5Y cells; PGC-1 alpha; RNA interference; ERR alpha
资金
- National Natural Science Foundation of China [81271414]
The dopaminergic neuron degeneration and loss that occurs in Parkinson's disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial function. Human peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1 alpha) is a multi-functional transcription factor that tightly regulates mitochondrial biogenesis and oxidative capacity. The goal of the present study was to explore the potential pathogenic effects of interference by the PGC-1 alpha gene on N-methyl-4-phenylpyridinium ion (MPP+)-induced SH-SY5Y cells. We utilized RNA interference (RNAi) technology to probe the pathogenic consequences of inhibiting PGC-1 alpha in the SH-SY5Y cell line. Remarkably, a reduction in PGC-1 alpha resulted in the reduction of mitochondrial membrane potential, intracellular ATP content and intracellular H2O2 generation, leading to the translocation of cytochrome c (cyt c) to the cytoplasm in the MPP+ -induced PD cell model. The expression of related proteins in the signaling pathway (e.g., estrogen-related receptor alpha (ERR alpha), nuclear respiratory factor 1 (NRF-1), NRF-2 and Peroxisome proliferator-activated receptor gamma (PPAR gamma)) also decreased. Our finding indicates that small interfering RNA (siRNA) interference targeting the PGC-1 alpha gene could inhibit the function of mitochondria in several capacities and that the PGC-1 alpha gene may modulate mitochondrial function by regulating the expression of ERR alpha, NRF-1, NRF-2 and PPAR gamma. Thus, PGC-1 alpha can be considered a potential therapeutic target for PD.
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