Butein restores mitochondrial homeostasis by inhibiting endoplasmic reticulum stress in endothelial cells
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 8
Abstract
Objective To investigate the protective effect of butein (BUT) on the vascular endothelial cells against oxidative stress-induced apoptosis by inhibiting the endoplasmic reticulum (ER) stress signaling pathway. Methods The hypoxia-induced oxidative stress injury model of human umbilical vein endothelial cells (HUVECs) was established. After being treated with different concentrations of BUT (2, 4, and 8 μmol / L) for 48 h, the cell viability was etermined by CCK-8 method, and the apoptotic cells were labeled by TUNEL staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential ( MMP) levels were detected by DCFH-DA and JC-1 staining, respectively. The main protein changes of ER stress and apoptosis pathways were detected by Western blotting. In addition, the above tests were repeated with an ER stress-specific agonist thapsigargin (Tg). Results Compared with the control group, hypoxic injury reduced cell viability and increased apoptosis. At the same time, MMP epolarization induced by hypoxic injury led to intracellular ROS accumulation. Molecular studies showed that hypoxic injury activated ER stress signaling pathway and up- regulated the expressions of apoptotic proteins. Different concentrations of BUT inhibited endothelial cell apoptosis, stabilized MMP level, cleared intracellular ROS accumulation, restored ER function, and finally reversed cell death in a “dose-dependent” manner (P <0. 05). The anti-hypoxic effect of BUT on endothelial cells was significantly decreased after Tg co-treatment (P < 0. 05). Conclusion BUT protects HUVECs from hypoxic injury by inhibiting ER stress signaling pathway and stabilizing mitochondrial function, thereby eliminating intracellular ROS accumulation and blocking apoptosis process.
Authors and Affiliations
FAN Chongxi, JIN Zhenxiao, NING Shoubin, ZHAI Meng'en, LI Bairong, XU Mengnan, CHEN Hongyu,ZHANG Jing, GUO Rui, YANG Quanlong, SHI Xuehui, FU Zhiguang
Keywords
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