Abstract
This study aimed to explore the effects of 2,3,5,4’-tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG) on the senescence of human umbilical vein cells (HUVEC) induced by hydrogen peroxide (H2O2) and to identify the potential targets mediating its protective action. HUVEC cells pre-treated with TSG for 24 h were exposed to H2O2 treatment. TSG significantly decreased H2O2-induced cellular senescence, as indicated by reduced senescence-associated β-galactosidase (SA-β-gal) positive staining, the proportion of cells in the G1 phase, cell apoptosis, p21, and plasminogen activator inhibitor-1 (PAI-1) expression. Moreover, TSG promoted Sirtuin 1 (SIRT1) expression. When SIRT1 was inhibited by EX527 or SIRT1 siRNA, the effect of TSG is diminished according to the increased proportion of cells in the G1 phase, cell apoptosis, p21, and PAI-1 expression. Overall, our study established TSG as an anti-senescence compound that exerts its protective action by regulating SIRT1 expression.
Highlights
Many studies have shown that endothelial cell senescence and dysfunction are the key factors leading to cardiovascular injury (Lin et al, 2017)
This study aimed to demonstrate whether TSG can relieve the human umbilical vein cells (HUVEC) senescence and investigate how Sirtuin 1 (SIRT1) functions in the process of HUVEC senescence when TSG is present
In order to more directly observe the effect of TSG on the expression of SIRT1 in HUVEC, immunofluorescence experiments were performed showing that TSG can significantly increase the fluorescence intensity associated with SIRT1 in senescent HUVEC, suggesting that TSG may block H2O2induced HUVEC senescence via SIRT1
Summary
Many studies have shown that endothelial cell senescence and dysfunction are the key factors leading to cardiovascular injury (Lin et al, 2017). Oxidative stress is a vital cause of endothelial dysfunction and senescence. Many age/longevity-related regulators have been described, such as Sirtuins (SIRTs), FOXO transcription factor, and mitogen-activated protein kinase (Harvey et al, 2015). Among the SIRT family, Sirtuin 1 (SIRT1) is currently thought to exert vascular protection and considered an anti-senescence molecule and is implicated in diverse cellular processes, including differentiation, senescence, apoptosis, metabolism, oxidative stress response, and inflammation (Michan and Sinclair, 2007; Yamakuchi and Lowenstein, 2009; Morris et al, 2011). Overexpression of SIRT1 in endothelial cells may prevent cellular senescence.the accurate mechanism of vascular aging is still largely unknown, and effective treatments are still lacking
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