蛋白激酶B
氧化应激
脂质过氧化
化学
内科学
药理学
内分泌学
医学
细胞凋亡
生物化学
作者
Jinhui Bian,Yi Ding,Song Wang,Yefan Jiang,Mingyan Wang,Ke Wei,Linjie Si,Xin Zhao,Yang Shao
标识
DOI:10.1016/j.freeradbiomed.2023.03.004
摘要
Obesity-induced cardiac dysfunction is a severe global disease associated with high dietary fat intake, and its pathogenesis includes inflammation, oxidative stress, and ferroptosis. Celastrol (Cel) is a bioactive compound isolated from the herb Tripterygium wilfordii, which has a protective influence on cardiovascular diseases. In this study, the role of Cel in obesity-induced ferroptosis and cardiac injury was investigated. We found that Cel alleviated ferroptosis induced by Palmitic acid (PA), exhibiting a decrease in the LDH, CK-MB, Ptgs2, and Lipid Peroxidation levels. After cardiomyocytes were treated with additional LY294002 and LiCl, Cel exerted its protective effect through increased AKT/GSK3β phosphorylation and decreased level of lipid peroxidation and Mitochondrial ROS. The systolic left ventricle (LV) dysfunction of obese mice was alleviated via ferroptosis inhibition by elevated p-GSK3β and decreased Mitochondrial ROS under Cel treatment. Moreover, mitochondrial anomalies included swelling and distortion in the myocardium which was relieved with Cel. In conclusion, our results demonstrate that ferroptosis resistance with Cel under HFD conditions targets AKT/GSK3β signaling, which provides novel therapeutic strategies in obesity-induced cardiac injury.
科研通智能强力驱动
Strongly Powered by AbleSci AI