Involvement of Flavonoids from the Leaves of Carya cathayensis Sarg. in Sirtuin 1 Expression in HUVEC Senescence.

Yan Guo,Zhishan Ding,Liwan Xing,Bo Jin,Chaodong Qian

doi:10.1155/2018/8246560

Yan Guo, Zhishan Ding + Show 3 more

Open Access

https://doi.org/10.1155/2018/8246560

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Abstract

Atherosclerosis is the commonest cause of death in the world and one of the most important processes that occurs with increasing age because it is accompanied by progressive endothelial dysfunction. Recent studies demonstrated that Sirtuin 1 (SIRT1) might potentially affect cell senescence. However, the effect of SIRT1 on the regulation of human umbilical vein endothelial cell (HUVEC) senescence with total flavonoids (TFs) has not been addressed previously. This study investigated how SIRT1 functions in the process of HUVEC senescence when TFs are present and identified the potential molecular mechanisms involved. Using a model of HUVEC senescence induced by angiotensin II, TFs pretreatment reduced the percentage of senescence-associated β-galactosidase (SA-β-gal) cells and p53 mRNA expression. The level of SIRT1 protein and E2F1 decreased during HUVEC senescence and could be partially recovered when cells were coincubated with TFs, while the levels of proteins p53 and p21 increased during cell senescence and diminished in response to the TFs treatment. When coincubated with 20 mM nicotinamide, the results with SA-β-gal-positive cells and the expression of SIRT1, E2F1, p53, and p21 were contrary to that obtained with only TFs pretreatment. The data indicate that the TFs exert their effect on HUVEC senescence through SIRT1.

Highlights

Atherosclerosis is the most widespread cause of death in the UK and is considered to be the most common cause of death in the world [1]
In order to further demonstrate whether the total flavonoids (TFs) could inhibit human umbilical vein endothelial cell (HUVEC) senescence, we selected the 5 μg/ml dose of TFs to explore the expression of p53 and p21
The levels of Sirtuin 1 (SIRT1) protein and E2F1 decreased during HUVEC senescence and could be partially recovered when cells were coincubated with TFs, while the levels of proteins p53 and p21 increased during cell senescence and diminished in response to the TFs treatment (Figures 4(e)–4(i))

Summary

Introduction

Atherosclerosis is the most widespread cause of death in the UK and is considered to be the most common cause of death in the world [1]. The incidence, prevalence, and mortality of atherosclerosis increase with age [1], and cellular senescence, genomic instability, and telomere attrition occur with increasing age [1]. Cellular senescence refers to the state of permanent cell cycle arrest when cells respond to exogenous and endogenous stress signals [3], including replicative senescence (RS) [4] and stress-induced premature senescence (SIPS) [5], which is characterized by a lack of proliferative activity and DNA damage markers [6]. Different cells have different cellular senescence characteristics and biomarkers, such as increased senescenceassociated beta-galactosidase (SA-β-gal) activity, cell cycle arrest [7], and increased p21 and p53 activity [8]. The tumor suppressor gene, p53, is involved in many aspects of cell biology, including cell proliferation, senescence, and death [8]

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