Role of Sirtuin-1 in Neonatal Hypoxic-Ischemic Encephalopathy and Its Underlying Mechanism

Abstract

Background Neonatal hypoxic-ischemic encephalopathy (HIE) is a dreaded disease and one of the leading causes of severe neurological dysfunction in neonates. The present study explored the functions of Sirtuin-1 (SIRT1) in neonatal HIE. Material/Methods A HIE neonatal rat model was generated to determine SIRT1 levels in brain tissues. Cell apoptosis and cell viability were analyzed by flow cytometry and MTT assay. qRT-PCR and Western blot analysis were used to assess gene mRNA and protein levels. Subsequently, the effect of SIRT1 on HIE was investigated in vitro by constructing an oxygen-glucose deprivation (OGD) cell model. Results The effective construction of the HIE rat model was confirmed by the enhanced brain cell apoptosis and the increased expression of HIE-related molecular markers, including S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE). SIRT1 expression was downregulated in HIE rat brain tissues. These findings indicated that SIRT1 was downregulated in neuronal cells subjected to OGD. In addition, enhanced cell viability and reduced cell apoptosis were observed, suggesting that SIRT1 overexpression relieved OGD-induced neuronal cell injury. Transfection with SIRT1-siRNA further increased OGD-induced neuronal cell injury, evidenced by decreased cell viability and enhanced cell apoptosis. Finally, SIRT1 overexpression significantly downregulated p-p65 protein expression. Conclusions Our findings revealed that SIRT1 may be a novel and promising therapy target for HIE treatment.

Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells

“…Using molecular docking simulations and cell-based studies, we herein demonstrated that both 4-dmH and heliomycin targeted SIRT1 and inhibited its activity and expression, to attenuate the growth of oral cancer cells. Given that SIRT1 contributes to a complex regulatory network, it is of primary importance to understand the fundamental regulatory mechanisms of SIRT1 in cell death regulation ( Wang et al, 2023 ; Wang et al, 2021a ; Lee et al, 2018 ; Zhu et al, 2020 ; Ran et al, 2023 ; Zhang et al, 2020 ).…”

Abnormal expression and role of MicroRNA‐214‐3p/SLC8A1 in neonatal Hypoxic‐Ischaemic encephalopathy

“…NSE, a glycolytic enolase enzyme, is present in the cytoplasm of cells with neuroendocrine differentiation and neurones in the brain. NSE levels can be indirectly estimated to determine the degree of neuronal damage and prognosis of neonatal HIE 26–28 . S100B—an acidic calcium‐binding protein in nervous tissues—is a potential biomarker to determine and evaluate minor brain damage of neonatal HIE 28,29 .…”

“…NSE levels can be indirectly estimated to determine the degree of neuronal damage and prognosis of neonatal HIE. 26 , 27 , 28 S100B—an acidic calcium‐binding protein in nervous tissues—is a potential biomarker to determine and evaluate minor brain damage of neonatal HIE. 28 , 29 Our results showed that the levels of brain injury‐related biomarkers, namely NSE and S100B, were increased in the brain tissue of neonatal HIE rats, indicating that HIE induced brain injury.…”

Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells

“…Using molecular docking simulations and cell-based studies, we herein demonstrated that both 4-dmH and heliomycin targeted SIRT1 and inhibited its activity and expression, to attenuate the growth of oral cancer cells. Given that SIRT1 contributes to a complex regulatory network, it is of primary importance to understand the fundamental regulatory mechanisms of SIRT1 in cell death regulation [57][58][59][60][61][62].…”