Suppression of Kv1.5 protects against endothelial apoptosis induced by palmitate and in type 2 diabetes mice

Publication date: 1 January 2017 Source:Life Sciences, Volume 168 Author(s): Jie-Yi Du, Feng Yuan, Li-Yan Zhao, Jie Zhu, Yun-Ying Huang, Gen-Shui Zhang, Yi Wei, Yun Liu, Quan Yi, Yong-sheng Tu, Xiao Zhong, Fang-Yun Sun, Hong-Shuo Sun, Yong-Yuan Guan, Wen-Liang Chen, Guan-Lei Wang Aims Palmitate, a common saturated free fatty acid, induces endothelial apoptosis in vitro in culture endothelial cells and in vivo in type 2 diabetes mellitus (T2DM) patients. The present study aimed to investigate whether Kv1.5 regulates palmitate-induced endothelial apoptosis and endothelial dysfunction in T2DM. Main methods In vitro experiments were carried out in primary human HUVECs. Apoptosis was analyzed by flow cytometry. Cell viability was determined by Cell Counting Assay Kit-8. The siRNA transfection was employed to knockdown Kv1.5 protein expression. Intracellular and mitochondrial ROS, and mitochondrial membrane potential were detected using fluorescent probes. Male C57BL/6 mice fed with high-sucrose/fat diet were injected with streptozotocin (35mg/kg body weight) to establish T2DM animal model. Key findings We found that palmitate-induced endothelial apoptosis was parallel to a significant increase in endogenous Kv1.5 protein expression in endothelial cells. Silencing of Kv1.5 with siRNA reduced palmitate-induced endothelial apoptosis, intracellular ROS generation, mitochondrial ROS generation and membrane potential (Δψm) alteration and cleaved caspase-3 protein e...
Source: Life Sciences - Category: Biology Source Type: research