EBBP-Mediated Integrated Stress Response Attenuates Anthracycline-Induced Cardiotoxicity by Inhibiting the Ferroptosis of Cardiomyocytes.

ABSTRACT: Anthracyclines are potent chemotherapeutics, but their clinical application is constrained by dose-dependent cardiotoxicity, in which ferroptosis plays a critical role. Here, EBBP (Estrogen-responsive B Box Protein) is identified as a key cardioprotective regulator in anthracycline-induced cardiotoxicity. Transcriptomic profiling of doxorubicin (DOX)-treated hearts reveals significant EBBP upregulation. Cardiac-specific overexpression of EBBP protects against myocardial injury and dysfunction by reducing DOX-induced ferroptosis. Conversely, EBBP silencing exacerbates DOX-induced cardiac damage, an effect reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). The molecular targets of EBBP are subsequently identified through bulk RNA sequencing, molecular docking analysis, co-immunoprecipi

SUBMITTER: Chen Z 

PROVIDER: S-EPMC12407386 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature