title: Dynamic mobilization of PGC-1α mediates mitochondrial biogenesis for the protection of RGC-5 cells by resveratrol during serum deprivation.
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.
authors.affiliation: Division of Glaucoma, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 54S Xianlie Road, 510060 Guangzhou, China.
authors.forename: Shida
authors.initials: S
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Fan
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Dongjiang
authors.initials: D
authors.lastname: Liao
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
authors.forename: Alan M
authors.initials: AM
authors.lastname: Laties
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects*; D009536:Niacinamide / Q000494:pharmacology; D051266:Nuclear Respiratory Factor 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D021381:Protein Transport / Q000187:drug effects; D000077185:Resveratrol; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D003470:Culture Media; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D013267:Stilbenes; C081930:Tfam protein, mouse; D014157:Transcription Factors; D009536:Niacinamide; D045304:Cytochromes c; C505409:Casp3 protein, mouse; D053148:Caspase 3; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol