Department of Cardiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China; Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Cardiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China; Department of Cardiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Mol Cell Endocrinol. 2025 Jan 1;595:112392. doi: 10.1016/j.mce.2024.112392. Epub 2024 Oct 23.
Selenoprotein M (SELENOM) has emerged as a crucial factor in maintaining cellular redox homeostasis and mitigating oxidative damage. This study aims to investigate its protective role in cardiac endothelial cells under hyperglycemic stress, a condition commonly associated with diabetes mellitus and its cardiovascular complications. Diabetic mice model and human umbilical vein endothelial cells (HUVECs) were applied for in vivo and in vitro studies. Results reveal that hyperglycemia significantly downregulates SELENOM expression in both diabetic mouse hearts and primary cultured cardiac endothelial cells. Overexpression of SELENOM in HUVECs mitigated high-glucose-induced FITC-Dextran diffusion and the loss of transendothelial electrical resistance. Additionally, SELENOM overexpression decreased reactive oxygen species (ROS) levels, preserved tight junction protein expression, and maintained cellular structural integrity under hyperglycemic conditions. Furthermore, SELENOM overexpression attenuated high-glucose-induced mitochondrial apoptosis. High-glucose conditions decreased Parkin and increased p62 and Beclin1 expressions. SELENOM overexpression restored Parkin levels and promoted co-localization of LAMP1 and TOMM20. Knockdown of Parkin significantly attenuated these protective effects, suggesting the importance of Parkin in Selenoprotein M-mediated mitophagy. Collectively, these findings suggest that Selenoprotein M enhances Parkin-mediated mitophagy to protect endothelial cells from hyperglycemic stress, offering potential therapeutic insights for diabetic cardiovascular complications.
硒蛋白 M（SELENOM）已成为维持细胞氧化还原稳态和减轻氧化损伤的关键因素。本研究旨在探讨其在高血糖应激下对心脏内皮细胞的保护作用，高血糖应激是糖尿病及其心血管并发症的常见情况。本研究应用糖尿病小鼠模型和人脐静脉内皮细胞（HUVEC）进行体内和体外研究。结果表明，高血糖显著下调糖尿病小鼠心脏和原代培养的心脏内皮细胞中 SELENOM 的表达。在 HUVEC 中过表达 SELENOM 可减轻高糖诱导的 FITC-Dextran 扩散和跨内皮电阻的丧失。此外，过表达 SELENOM 可降低活性氧（ROS）水平，在高糖条件下维持紧密连接蛋白表达和细胞结构完整性。此外，过表达 SELENOM 可减轻高糖诱导的线粒体凋亡。高糖条件下 Parkin 表达降低，p62 和 Beclin1 表达增加。过表达 SELENOM 可恢复 Parkin 水平并促进 LAMP1 和 TOMM20 的共定位。Parkin 敲低显著减弱了这些保护作用，表明 Parkin 在 SELENOM 介导的线粒体自噬中的重要性。综上所述，这些发现表明，硒蛋白 M 通过增强 Parkin 介导的线粒体自噬来保护内皮细胞免受高血糖应激，为糖尿病心血管并发症的治疗提供了潜在的思路。
