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

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 and SIRT1/HIF-1α signaling, which may serve as a clue for understanding PD.

SIRT1 mediates salidroside‐elicited protective effects against MPP+‐induced apoptosis and oxidative stress in SH‐SY5Y cells: involvement in suppressing MAPK pathways

“…Recently, the neuroprotective properties of SIRT1 have also been described in PD depending on anti‐apoptotic and anti‐oxidant features (Tsai et al, ; Zou et al, ). In present study, we found that MPP + treatment obviously decreased the SIRT1 activity, SIRT1 mRNA and protein levels in SH‐SY5Y cells, which is also consistent with the research done by Dong et al (), Tao et al (), and Zou et al (). Remarkably, some researchers reveal that SIRT1 contributes to the protective effects of salidroside against kainic acid‐induced status epilepticus (Si et al, ), d ‐galactose‐induced rat model of Alzheimer's disease (AD) (Gao et al, ), and hypoxia‐induced neurodegeneration (Barhwal et al, ).…”

“…Its beneficial effects are widely explored in neurodegenerative diseases, including PD (Ramadori et al, 2008). Numerous studies have revealed that SIRT1 level in dopaminergic neurons is obviously down-regulated in toxic models of PD (Pallas et al, 2008;Albani et al, 2009;Donmez and Outeiro, 2013), and SIRT1 overexpression or activation attenuates neuronal death as well as neurodegeneration in both vivo and vitro PD models (Albani et al, 2009;Dong et al, 2016). Notably, previous studies suggested that multiple signaling pathways including phosphoinositide 3-kinase (PI3K), MAPKs, and other pathways are associated with the neuroprotection of SIRT1 (Zhang et al, 2016b;Yang et al, 2017).…”

Upregulation of miR‐200a and miR‐204 in MPP+‐treated differentiated PC12 cells as a model of Parkinson’s disease

“…Here, mRNA level of Sirt1 was found (Figure 5a). Consistently, the level of Sirt1 is markedly downregulated in toxic models of PD (Dong et al, 2016;Pallas et al, 2008). In contrast, levels of SIRT1 increase as a protective response to neurodegenerative conditions in some models of neurodegeneration (Kim et al, 2007).…”

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

“…Two research groups have described morphological and gene expression changes in this cell line in stiff environments [53,54]. It is possible that ALK-mutated cells respond to ECM changes through epigenetic alterations or genetic mutations undetected by the techniques we employed [53,[75][76][77].…”