Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells.

ABSTRACT: 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 ? coactivator-1alpha (PGC-1?) 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? 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? in the SH-SY5Y cell line. Remarkably, a reduction in PGC-1? 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 ? (ERR?), nuclear respiratory factor 1 (NRF-1), NRF-2 and Peroxisome proliferator-activated receptor ? (PPAR?)) also decreased. Our finding indicates that small interfering RNA (siRNA) interference targeting the PGC-1? gene could inhibit the function of mitochondria in several capacities and that the PGC-1? gene may modulate mitochondrial function by regulating the expression of ERR?, NRF-1, NRF-2 and PPAR?. Thus, PGC-1? can be considered a potential therapeutic target for PD.

SUBMITTER: Ye Q 

PROVIDER: S-EPMC5447087 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature