SIRT3 通过 p53 通路保护内皮细胞免受高糖诱导的衰老和功能障碍。
SIRT3 protects endothelial cells from high glucose-induced senescence and dysfunction via the p53 pathway.
机构信息
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Radiology, Qilu Hospital of Shandong University, Jinan, China.
出版信息
Life Sci. 2021 Jan 1;264:118724. doi: 10.1016/j.lfs.2020.118724. Epub 2020 Nov 5.
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.
高血糖通过加速内皮细胞衰老诱导内皮细胞功能障碍和血管并发症。它还会下调沉默调节蛋白（SIRTs）。然而，SIRT3 调节内皮细胞衰老的分子机制尚不清楚。在这里，我们表明，高葡萄糖（HG）降低了人脐静脉内皮细胞（HUVECs）中 SIRT3 的表达水平，增加了表达衰老相关半乳糖苷酶（SA-gal）的细胞比例，并且 HG 损害了细胞在 Matrigel 上形成管状网络的能力。然而，转染包含 SIRT3 的腺病毒构建体可显著抑制 HG 诱导的 SA-gal 活性，降低 p53 在赖氨酸 320 位（k320）的乙酰化水平，并且 SIRT3 的过表达拮抗高葡萄糖诱导的血管生成功能障碍。我们的结果表明，在 ECs 衰老中可能存在涉及 HG-SIRT3-p53 的分子机制。
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