Dynamic mobilization of PGC-1α mediates mitochondrial biogenesis for the protection of RGC-5 cells by resveratrol during serum deprivation

Shida Chen; Qian Fan; Ang Li; Dongjiang Liao; Jian Ge; Alan M Laties; Xiulan Zhang

doi:10.1007/s10495-013-0837-3

Dynamic mobilization of PGC-1α mediates mitochondrial biogenesis for the protection of RGC-5 cells by resveratrol during serum deprivation

Apoptosis. 2013 Jul;18(7):786-99. doi: 10.1007/s10495-013-0837-3.

Authors

Shida Chen¹, Qian Fan, Ang Li, Dongjiang Liao, Jian Ge, Alan M Laties, Xiulan Zhang

Affiliation

¹ Division of Glaucoma, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 54S Xianlie Road, 510060 Guangzhou, China.

PMID: 23525928
DOI: 10.1007/s10495-013-0837-3

Abstract

Mitochondrial dysfunction contributing to the pathogenesis of glaucomatous neurodegeneration has stimulated considerable interest recently. In this study, we explored the role of peroxisome proliferator activated receptor-γ co-activator 1α (PGC-1α) in resveratrol-triggered mitochondrial biogenesis for preventing apoptosis in a retinal ganglion cell line RGC-5. Our results showed that serum deprivation induced cell apoptosis in a time-dependent manner. Applying resveratrol maintained the normal mitochondrial membrane potential, decreased the levels of both total and cleaved caspase-3, and inhibited the release of cytochrome c, which subsequently enhanced cell survival. Moreover, resveratrol stimulated mitochondrial biogenesis by increasing the absolute quantity of mitochondria as well as their DNA copies. Treatment with resveratrol promoted the protein expression of SIRT1, but not PGC-1α; instead, resveratrol facilitated PGC-1α translocation from the cytoplasm to the nucleus and up-regulated NRF1 and TFAM, which were blocked by nicotinamide. Collectively, we demonstrate that the SIRT1-dependent PGC-1α subcellular translocation following resveratrol application potentially attenuates serum deprivation-elicited RGC-5 cell death, thereby raising the possibility of mitigating glaucomatous retinopathy by enhancement of mitochondrial biogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caspase 3 / genetics
Caspase 3 / metabolism
Cell Line
Cell Survival / drug effects
Culture Media / chemistry
Cytochromes c / metabolism
DNA-Binding Proteins / agonists
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Gene Expression Regulation
High Mobility Group Proteins / agonists
High Mobility Group Proteins / genetics
High Mobility Group Proteins / metabolism
Membrane Potential, Mitochondrial / drug effects
Mice
Mitochondria / drug effects*
Mitochondria / genetics
Mitochondria / metabolism
Mitochondrial Turnover / drug effects*
Niacinamide / pharmacology
Nuclear Respiratory Factor 1 / agonists
Nuclear Respiratory Factor 1 / genetics
Nuclear Respiratory Factor 1 / metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Protein Transport / drug effects
Resveratrol
Retinal Ganglion Cells / cytology
Retinal Ganglion Cells / drug effects*
Retinal Ganglion Cells / metabolism
Signal Transduction
Sirtuin 1 / genetics
Sirtuin 1 / metabolism
Stilbenes / pharmacology*
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

Culture Media
DNA-Binding Proteins
High Mobility Group Proteins
Nrf1 protein, mouse
Nuclear Respiratory Factor 1
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Ppargc1a protein, mouse
Stilbenes
Tfam protein, mouse
Transcription Factors
Niacinamide
Cytochromes c
Casp3 protein, mouse
Caspase 3
Sirt1 protein, mouse
Sirtuin 1
Resveratrol