Liu Guodong, Cao Mingming, Xu Ying, Li Yanbo
Department of Endocrine, The First Affiliated Hospital of Harbin Medical University 23 Youzheng Str, Harbin 150001, P.R. China.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):353-60. eCollection 2015.
Diabetes is a frequent and increasing public health problem with a large economic burden in modern society. Endothelial cells dysfunction was involved in the development of diabetes-associated diseases. Sirtuins are a conserved family of NAD-dependent deacetylases. However, the role of sirtuins in diabetes-associated endothelial cell dysfunction was relatively unknown. In this study, we focus on the intrinsic link between SIRT3, a mitochondrial sirtuin, and high glucose-induced endothelial cells dysfunction. We showed that loss of SIRT3 expression was associated with decreased viability in endothelial cells from diabetes patients. Knockdown of SIRT3 decreased viability of endothelia cells exposed to high glucose condition. Further, mechanistic study showed that SIRT3 repression results in SOD2 acetylation, leading to SOD2 inactivation, which enhanced high glucose-induced oxidative stress in endothelial cells. Our data suggested that SIRT3 protects endothelial cells from high glucose-induced cytotoxicity. Our findings are considered a significant step toward a better understanding of diabetes-associated vascular diseases.
糖尿病是现代社会中一个常见且日益严重的公共卫生问题，经济负担巨大。内皮细胞功能障碍参与了糖尿病相关疾病的发生发展。沉默调节蛋白是一类保守的依赖烟酰胺腺嘌呤二核苷酸（NAD）的去乙酰化酶家族。然而，沉默调节蛋白在糖尿病相关内皮细胞功能障碍中的作用相对未知。在本研究中，我们聚焦于线粒体沉默调节蛋白SIRT3与高糖诱导的内皮细胞功能障碍之间的内在联系。我们发现，糖尿病患者内皮细胞中SIRT3表达缺失与细胞活力降低有关。敲低SIRT3会降低暴露于高糖环境下的内皮细胞活力。此外，机制研究表明，SIRT3表达受抑制会导致超氧化物歧化酶2（SOD2）乙酰化，进而导致SOD2失活，增强了高糖诱导的内皮细胞氧化应激。我们的数据表明，SIRT3可保护内皮细胞免受高糖诱导的细胞毒性。我们的研究结果被认为是朝着更好地理解糖尿病相关血管疾病迈出的重要一步。
