Quercetin Improves Cardiomyocyte Vulnerability to Hypoxia by Regulating SIRT1/TMBIM6‐Related Mitophagy and Endoplasmic Reticulum Stress

作者：Xing Chang, Tian Zhang, Qingyan Meng, ShiyuanWang, Peizheng Yan, Xue Wang, Duosheng Luo, Xiuteng Zhou, Ruifeng Ji · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2021 · DOI：10.1155/2021/5529913 · 被引用次数：118 · 研究领域：Autophagy in Disease and Therapy、Adipose Tissue and Metabolism、Sirtuins and Resveratrol in Medicine

Cardiomyocyte apoptosis is an important pathological mechanism underlying cardiovascular diseases and is commonly caused by hypoxia. Moreover, hypoxic injury occurs not only in common cardiovascular diseases but also following various treatments of heart‐related conditions. One of the major mechanisms underlying hypoxic injury is oxidative stress. Quercetin has been shown to exert antioxidant stress and vascular protective effects, making it a promising candidate for treating cardiovascular diseases. Therefore, we examined the protective effect of quercetin on human cardiomyocytes subjected to hypoxia‐induced oxidative stress damage and its underlying mechanism. Human cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro with or without quercetin pretreatment; thereafter, flow cytometry, Cell Counting Kit‐8 assay, laser scanning confocal microscopy, quantitative PCR, western blotting, and enzyme‐linked immunosorbent assay were performed to analyze the effects of quercetin on cardiomyocytes. We found that H/R induced reactive oxygen species overproduction and endoplasmic reticulum stress, as well as inhibited the function of the mitochondria/endoplasmic reticulum and mitophagy, eventually leading to apoptosis and decreasing the viability of human cardiomyocytes. Quercetin pretreatment inhibited H/R‐mediated overproduction of reactive oxygen species and damage caused by oxidative stress, increased mitophagy, regulated mRNA and protein expression of transmembrane...