Effects Of PGC-1α Deacetylation On MPP~+-induced Oxidative Damage In SH-SY5Y Cells

BackgroundIn recent years, it was found that PPARγcoactivator-1α(PGC-1α） plays an animportant role on mitochondrial biology and oxidative stress, and can regulateextremly the process of antioxidation. PGC-1α stimulate genes involved inmitochondrial biogenesis, energe matabelism, fatty acid oxidation and hepaticgluconeogenesis. The transcription activity of PGC-1α is regulated by SIRT1, aendogenous deacetyltransferase. It has not yet been reported about the mechanisms ofSIRT1on MPP~+-induced oxidative stress in SH-SY5Y cells, whether SIRT1plays aprotection role of MPP~+-induced oxidative stress in SH-SY5Y cells, via the SIRT1/PGC-1α axis.ObjectiveTo elucidate the effects of PGC-1α deacetylated by SIRT1on MPP~+-inducedcytotoxicity in SH-SY5Y cells. To elucidate the effects of PGC-1α deacetylation onMPP~+-induced oxidative damage in SH-SY5Y cells and the molecular mechanismsamong this.MethodsSH-SY5Y cells treated with MPP~+were used as in vitro cell model. Cellimmunohistochemical was used to investigate TH neuron. MTT assay was used toinvestigate the effects of MPP~+, SRT1720and EX527on SH-SY5Y cell viability.SH-SY5Y intracellular ROS production was detected via Flow cytometry analysis technic.Western-Blot analysis was used to observe the protein expression of SIRT1, PGC-1α.ResultsSH-SY5Y cell viability was significantly decreased in the groups treated by the MPP~+.Respectively, SRT1720、EX527treated group which is under a certain range, cell viability have no change. SRT1720、EX527decreased the generation of ROS induced by MPP~+. Theprotein of SIRT1、PGC-1α were decreased by MPP~+-induced(P<0.05). Pretreated byEX527, the SIRT1、PGC-1α expression was increased (P<0.05), pretreated, by SRT1720,the SIRT1、PGC-1α expression was no changed.ConclusionsEX527is not the inhibitor of SIRT1on MPP~+-induced SH-SY5Y cells model, incontrast EX527can increase the activity of SIRT1. SRT1720is not the activator ofSIRT1on this cell model. SIRT1plays a protection role of MPP~+-induced oxidasestress in SH-SY5Y cells, via enhancing PGC-1α deacetylation and inhibiting ROSproduction.