Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11/GSH/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation.

ABSTRACT: Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H₂S) is emerging as the third important gaseous mediator in cardiovascular system. However, whether H₂S has an effect on DOX-induced ferroptosis remains unknown. Here, we found that DOX not only triggered cardiomyocyte ferroptosis but also significantly inhibited the synthesis of endogenous H₂S in the murine model of chronic DoIC. Application of NaHS, an H₂S donor obviously activated the SLC7A11/GSH/GPx4 antioxidant pathway and thus alleviated DOX-induced ferroptosis and cardiac injury in mice. In contrast, cardiac-specific knockout of cystathionine γ-lya

SUBMITTER: Zhang H 

PROVIDER: S-EPMC10877437 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature