201. [Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6.
- Author
-
Li M, Liu Z, Cao X, Xiao W, Wang S, Zhao C, Zhao Y, and Xie Y
- Subjects
- Humans, Intracellular Signaling Peptides and Proteins metabolism, Sirtuins metabolism, Cellular Senescence drug effects, Glucose metabolism, Reactive Oxygen Species metabolism, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism
- Abstract
High glucose (HG) induced endothelial senescence is related to endothelial dysfunction and cardiovascular complications in diabetic patients. Humanin, a member of mitochondrial derived peptides (MDPs), is thought to contribute to aging-related cardiovascular protection. The goal of the study is to explore the pathogenesis of HG-induced endothelial senescence and potential anti-senescent effects of Humanin. Human umbilical vein endothelial cells (HUVECs) were exposed to glucose to induce senescence, determined by β-galactosidase staining and the expressions of p21, p53, and p16. A clinically relevant dose of HG (15 mM, HG) induced endothelial senescence after 72 h incubation without elevated apoptosis. HG-induced senescence was attributed to the induction of reactive oxygen species (ROS) caused by SIRT6 downregulation, as ROS inhibitor N-acetyl cysteine blocked HG-induced senescence, while inactivation of SIRT6 increased ROS levels and promoted senescence. Strikingly. pretreatment with [Gly14]-Humanin (HNG) antagonized the downregulation of SIRT6 in response to HG and alleviated ROS production and cell senescence. HG-induced reduction of SIRT6 results in ROS overproduction and endothelial senescence. Humanin protects against HG-induced endothelial senescence via SIRT6. This study provides new directions for biological products related to Humanin to be a potential candidate for the prevention of vascular aging in diabetes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University (JD-LK-2022-095-01, July 28, 2022). Consent to participate: All methods in this study were conducted according to the guidelines and regulations of the Declaration of Helsinki, and all informed consent was obtained from all subjects and/or their legal guardian(s)., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF