title: Epigallocatechin-3-gallate suppresses 1-methyl-4-phenyl-pyridine-induced oxidative stress in PC12 cells via the SIRT1/PGC-1α signaling pathway.
abstract: BACKGROUND
  Parkinson's disease is a high incidence neurodegenerative disease in elderly people, and oxidative stress plays an important role in the pathogenesis. Oxygen metabolism in the brain is high, which lacks an antioxidative protection mechanism. Recently, it has been found that polyphenols play an important role in antioxidation. (-)-epigallocatechin-3-gallate (EGCG) is an important component of tea polyphenols and its biological effects, such as strong antioxidation, scavenging of free radicals and anti-apoptosis, can pass through the blood brain barrier. The SIRT1/PGC-1α signaling pathway has not been reported in PC12 cells. Therefore, research of the protective mechanism of EGCG in PC12 cells damaged by -methyl-4-phenyl-pyridine (MMP+) may provide a new insight into protect against and treatment of Parkinson's disease.
  
  
  METHODS
  MPP(+)-treated highly differentiated PC12 cells were used as the in vitro cell model. An MTT assay was used to investigate cell viability after EGCG treatment, a dichlorofluorescin diacetate assay was used to measure reactive oxygen species (ROS) production, western blot analysis was used to observe PGC-1α and SIRT1 protein expression, and real-time PCR to observe PGC-1α, SOD1 and GPX1 mRNA expression.
  
  
  RESULTS
  PC12 cell viability was significantly reduced after MPP(+) treatment by 11.46% compared with that of the control (P < 0.05). However, cell viability was unchanged by 10 μmol/L EGCG treatment. In co-treatments with EGCG and MPP(+), cell viability was significantly increased by 12.92% (P < 0.05) and MPP(+)-induced ROS production was markedly decreased. PGC-1α mRNA expression was obviously upregulated by 21.51% (P < 0.05), and SOD1 and GPX1 mRNA expression was slightly increased by 12.94% and 15.63% (P > 0.05), respectively, by treatment with EGCG and then MPP(+) for 12 h. The mRNA expression of PGC-1α, SOD1 and GPX1 was increased by 25.17%, 40% and 146% (all P < 0.05), respectively, by treatment with EGCG and then MPP(+) for 24 h. Such effects were not observed with MPP(+) treatment alone.
  
  
  CONCLUSIONS
  The SIRT1/PGC-1α pathway is one of the mechanisms of EGCG suppression of MPP(+)-induced injury of PC12 cells.
authors: Department of Neurology, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China. unionqyye@163.com
authors: Qinyong
authors: Q
authors: Ye
authors: Linfeng
authors: L
authors: Ye
authors: Xianjie
authors: X
authors: Xu
authors: Bixia
authors: B
authors: Huang
authors: Xiaodong
authors: X
authors: Zhang
authors: Yuangui
authors: Y
authors: Zhu
authors: Xiaochun
authors: X
authors: Chen
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013662:Tea / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D013662:Tea; D014157:Transcription Factors; D002392:Catechin; C045651:epigallocatechin gallate; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D015655:1-Methyl-4-phenylpyridinium; D000094765:Glutathione Peroxidase GPX1