SLC7A11/GPX4 Inactivation-Mediated Ferroptosis Contributes to the Pathogenesis of Triptolide-Induced Cardiotoxicity.

ABSTRACT: Triptolide exhibits promising efficacy in various cancers and immune diseases while its clinical application has been strongly restricted by its severe side effects, especially cardiotoxicity. However, the underlying mechanism of triptolide-induced cardiotoxicity (TIC) remains unclear. The RNA-seq analysis of triptolide-injured AC16 human cardiomyocyte cell line hinted that ferroptosis is involved in TIC. Further experimental validations proved that triptolide triggered ferroptosis, as evidenced by significant accumulation of lipid peroxidation (4-HNE and MDA levels) and ferrous iron, as well as depletion of intracellular GSH. Furthermore, triptolide-induced iron overload involved the upregulation of TF/TRFC/DMT1 signal axis and the degradation of ferritin, which contribute to ROS generati

SUBMITTER: Liu X 

PROVIDER: S-EPMC9225845 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature