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EGCG Protects PC12 Cells Against Oxidative Toxicity Through SIRT1/PGC-1α Pathways

Posted on:2012-09-08Degree:MasterType:Thesis
Country:ChinaCandidate:L F YeFull Text:PDF
GTID:2154330335477345Subject:Neurology
Abstract/Summary:
Background and Purpose PD is a high incidence of neurodegenerative diseases in elderly people, and oxidatie stress plays an important role in PD pathogenesis mechanism. Brain is a high oxygen metabolism rate tissue, and lack of antioxidant protection mechanism. In recent years,it found that polyphenols mostly play an an important role in antioxidation and antiradical. EGCG is an important component of tea polyphenols, it has biological effects such as strong antioxidant injury, scavenging free radicals and antiapoptotic, and can through the blood brain barrier smoothly. SIRT1/PGC-1αcell signaling pathways was not been reported in PC12 cell. Therefore, research the mechanism of EGCG protect PC12 cell damage by MPP + will p rovide a new idea to protect and treatment of PD.Objective To investigate effect of EGCG on MPP~+-induced cell viability loss in cultured PC12 cells. To explore the effect of EGCG on expression level of PGC-1α,SIRT1,SOD1,GPX1 in MPP~+-induced PC12 cells.Methods Cell viability was measured by methylthiazolyltetrazolium(MTT)assay after PC12 cells were treated with various concentrations of EGCG(2.5,5,10,20,40umol/L)and/or MPP~+(125,250,500,1000,2000umol/L)for 24 hours in vitro. The protein expression level of PGC-1αand SIRT1 were detected by western after the PC12 cells were incubated with EGCG(10umol/L)and/or MPP~+ (500μmol/L)for 24 hours in vitro.The mRNA expression level of SOD1 and GPX1 were detected by Real time PCR after the PC12 cells were incubated with EGCG(10umol/L)and/or MPP~+ (500μmol/L)for 24 hours in vitro.Results Compared with control group,the survival percent of PC12 cells were significantly decreased in 250 to 2000μmol/L MPP~+-treated group.The neurotoxic effect of MPP~+ were significantly decreased by EGCG,when the cells were co-incubated with MPP~+ and different concentrations of EGCG for 24h. Compared with control group,the level of PGC-1αand SIRT1 protein expression in MPP~+ co-incubuted with EGCG group were significantly increasead . Compared with control group,the level of SOD1 and GPX1 mRNA expression in MPP~+ co-incubuted with EGCG group were significantly increasead .Conclusions EGCG exhibited neuroprotective effect on the MPP~+-induced cytotoxicity in adose-dependent manner in the PC12 cells. EGCG upregulated the expression of PGC-1α,SIRT1,SOD1,GPX1 in MPP~+-induced PC12 cells.
Keywords/Search Tags:Parkinson's Disease, PC12 cell, Epigallocatechin-3-gallate, Peroxisomal proliferator-activated receptor-coactivator 1, 1-methyl-4-phenylpyridiniumion, Silent mating type information regulation 2 homolog 1
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