The Expression And Regulation Mechanism Of HIF-1? In MPP~+ Treated SH-SY5Y Cells

Both silent information regulator 1(SIRT1)and hypoxia inducible factor 1(HIF-1)have been found to play important roles in the pathophysiology of Parkinson's disease(PD).However,the mechanisms still require further study.Several studies have been carried out to explore the relationship between SIRT1 and HIF-1,howerver,there are still no consistent conclusions on it.In the present study,to explore the change and relationship of SIRT1 and HIF-1?in PD,the SH-SY5Y cells were treated with MPP~+to establish PD models in vitro.In our study,MPP~+induced the inhibition of cell proliferation,cell cycle arrest and apoptosis.Meanwhile,we found that the expression level of HIF-1?and its target genes including VEGFA and LDHA were increased.Our former study had demonstrated that SIRT1 expression was inhibited in PD models.In the present study,we have confirmed the results again.As it is a histone deacetylase,we used Chromatin Immunoprecipitation(ChIP)to observe the histone modification of HIF-1?,the acetylation of H3K14 combined with the HIF-1?promoter was dramatically increased in cells treated with MPP~+,which resulted in the transcriptional activation of HIF-1?.Moreover,the acetylation of H3K14and the expression of HIF-1?increased when SIRT1 was knocked down,suggesting that SIRT1 is involved in the epigenetic regulation of HIF-1?.Therefore,our results support a link between PD and SIRT1/HIF-1?signaling,which may serve as a clue for understanding PD.