The epigenetic regulation of HIF-1α by SIRT1 in MPP(+) treated SH-SY5Y cells

Biochemical and Biophysical Research Communications
Su-Yan DongYun-Cheng Wu

Abstract

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, their mechanisms and their relationship still require further study. In the present study, we focused on the change and relationship of SIRT1 and HIF-1α in PD. PD cell models were established by using methyl-4-phenylpyridinium (MPP(+)), which induced inhibition of cell proliferation, cell cycle arrest and apoptosis. We found that the expression of HIF-1α and its target genes VEGFA and LDHA increased and that SIRT1 expression was inhibited in MPP(+) treated cells. With further analysis, we found that the acetylation of H3K14 combined with the HIF-1α promoter was dramatically increased in cells treated with MPP(+), which resulted in the transcriptional activation of HIF-1α. Moreover, the acetylation of H3K14 and the expression of HIF-1α increased when SIRT1 was knocked down, suggesting that SIRT1 was involved in the epigenetic regulation of HIF-1α. At last, phenformin, another mitochondrial complex1 inhibitor, was used to testify that the increased HIF-1a was not due to off target effects of MPP(+). Therefore, our results support a link between PD a...Continue Reading

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Citations

Feb 6, 2017·Biochemical and Biophysical Research Communications·Xin-Xin CuiYun-Cheng Wu
Mar 7, 2017·General and Comparative Endocrinology·Ying LinYing Xing
Feb 4, 2019·Molecular Genetics & Genomic Medicine·Maryam Talepoor ArdakaniKamran Ghaedi
Oct 18, 2018·International Immunology·Amit Singhal, Catherine Youting Cheng
Oct 17, 2017·Cellular and Molecular Life Sciences : CMLS·Weibo Luo, Yingfei Wang
Feb 15, 2018·Journal of Alzheimer's Disease : JAD·Niraj Kumar JhaPravir Kumar
Oct 3, 2020·International Journal of Molecular Sciences·Rui WangHaigang Ren
Jul 8, 2017·Antioxidants & Redox Signaling·Nathalie KhouryMiguel A Perez-Pinzon
Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Amparo López-CarrascoRosa Noguera
Feb 19, 2021·Frontiers in Pharmacology·Ramu ManjulaFrancisco J Alcain
May 1, 2018·American Journal of Human Genetics·Dong WangYong-Gang Yao

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