Molecular Neurobiology

, Volume 53, Issue 6, pp 3756–3770 | Cite as

Overexpression of PGC-1α Influences Mitochondrial Signal Transduction of Dopaminergic Neurons

  • Qinyong Ye
  • Wanling Huang
  • Dongzhu Li
  • Erwang Si
  • Juhua Wang
  • Yingqing Wang
  • Chun Chen
  • Xiaochun Chen
Article

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease in the elderly. Mitochondrial dysfunction plays an important role in the pathogenesis of PD. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a powerful transcription factor, interacting with multiple transcription factors and widely involving in the regulation of mitochondrial biogenesis, oxidative stress, and other processes. The present study investigated the neuroprotective effects and signal transduction mechanisms of the overexpression of PGC-1α on N-methyl-4-phenylpyridinium ion (MPP+)-induced mitochondrial damage in SH-SY5Y cell, establishing the cell model of overexpression of PGC-1α and the cell model of PD by using adenoviral vectors and MPP+. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was used to investigate the effects of MPP+ and adenovirus on the cell viability of SH-SY5Y cells and the cell viability of experimental groups. Western blot and real-time PCR analysis were used to detect the expression of PGC-1α. Flow cytometry and ELISA were used to detect mitochondrial membrane potential and the level of cytochrome C, respectively. The level of intracellular ATP and H2O2 was measured by multifunctional fluorescence microplate. Western blot analysis and real-time PCR were used to observe the expression of estrogen-related receptor α (ERRα), peroxisome proliferator-activated receptor γ (PPARγ), nuclear respiratory factor (NRF)-1, and NRF-2. Confocal fluorescence analysis was used to observe subcellular localization of PGC-1α in SH-SY5Y cells under the intervention of MPP+. The expression of PGC-1α messenger RNA and protein significantly increased in Adv-PGC-1α + GFP groups, compared with the control and Adv-GFP groups (P < 0.01). The overexpression of PGC-1α could increase mitochondrial membrane potential, reduce the release of mitochondrial cytochrome C, inhibit H2O2 production, and improve the level of ATP in SH-SY5Y cells. The trend of expression of ERRα, PPARγ, and NRF-1 was more consistent with PGC-1α, the most remarkable change is ERRα, but the expression of NRF-2 has no significant changes. Under the gradually increasing concentration of MPP+, microscale PGC-1α gradually appeared in the cytoplasm of SH-SY5Y cells. The overexpression of PGC-1α can inhibit MPP+-induced mitochondrial damage in SH-SY5Y cells, and PGC-1α may realize the neuroprotective effects via the ERRα, PPARγ, and NRF-1 pathway.

Keywords

Parkinson’s disease PGC-1α Adenovirus vector SH-SY5Y cells Nuclear transcription factors 

Abbreviations

PGC-1α

Peroxisome proliferator-activated receptor-γ coactivator-1α

MPP+

N-methyl-4-phenylpyridinium ion

NRF-1/2

Nuclear respiratory factor 1/2

ERRα

Estrogen-related receptor α

PPARγ

Peroxisome proliferator-activated receptor γ

Cyt C

Cytochrome C

TFAM

Mitochondrial transcription factor A

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Qinyong Ye
    • 1
  • Wanling Huang
    • 1
  • Dongzhu Li
    • 1
  • Erwang Si
    • 1
  • Juhua Wang
    • 1
  • Yingqing Wang
    • 1
  • Chun Chen
    • 1
  • Xiaochun Chen
    • 1
  1. 1.Department of Neurology, Fujian Institute of GeriatricsThe Affiliated Union Hospital of Fujian Medical UniversityFuzhouChina

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