SIRT3 protects endothelial cells from high glucose-induced senescence and dysfunction via the p53 pathway

被引：35

作者：

Chen, Tongshuai ^{[1
,2
]}

Ma, Chang ^{[1
,2
]}

Fan, Guanqi ^{[1
,2
,3
]}

Liu, Hui ^{[1
,2
]}

Lin, Xie ^{[1
,2
]}

Li, Jingyuan ^{[1
,2
]}

Li, Na ^{[1
,2
]}

Wang, Shujian ^{[1
,2
]}

Zeng, Mei ^{[1
,2
]}

Zhang, Yun ^{[1
,2
]}

Bu, Peili ^{[1
,2
]}

机构：

[1] Shandong Univ, Chinese Natl Hlth Commiss, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Jinan, Peoples R China

[2] Shandong Univ, Chinese Acad Med Sci, State & Shandong Prov Joint Key Lab Translat Card, Dept Cardiol,Qilu Hosp,Cheeloo Coll Med, Jinan, Peoples R China

[3] Shandong Univ, Dept Radiol, Qilu Hosp, Jinan, Peoples R China

来源：

LIFE SCIENCES | 2021年 / 264卷

基金：

中国国家自然科学基金;

关键词：

High glucose; Endothelial senescence; SIRT3; p53; CELLULAR SENESCENCE; PROLIFERATION; ACETYLATION; EXPRESSION; APOPTOSIS; PROTEINS; SIRTUINS; GROWTH;

D O I：

10.1016/j.lfs.2020.118724

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Hyperglycemia induces endothelial cells (ECs) dysfunction and vascular complications by accelerating ECs senescence. It also induces downregulation of sirtuins (SIRTs). However, the molecular mechanism involved in the regulation of ECs senescence by SIRT3 remains unclear. Here, we showed that high glucose (HG) decreased the expression level of SIRT3 in human umbilical vein endothelial cells (HUVECs), increased the proportion of cells expressing senescence-associated galactosidase (SA-gal), and HG damaged the cell's ability to form tubule networks on Matrigel. However, transfection with adenoviral construct including SIRT3 significantly inhibited HG-induced SA-gal activity, decreased p53 acetylation level at the site Lys 320 (k320), and overexpression of SIRT3 antagonized high glucose-induced angiogenic dysfunction. Our results suggested a possible molecular mechanism involving HG-SIRT3-p53 in ECs senescence.

引用

页数：9

共 41 条

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