Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11/GSH/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation
Shanghai Jiao Tong University · Fudan University · +3 more institutions
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,…
Citation impact
- FWCI
- 49.55
- Percentile
- 100%
- References
- 53
Authors
10- HZHui Zhang
Shanghai Jiao Tong University, Fudan University, Shanghai Ninth People's Hospital, Zhongshan Hospital, Shanghai Institute of Hematology
- HZHui ZhangCorresponding
Shanghai Jiao Tong University, Shanghai Ninth People's Hospital
- JPJianan Pan
Shanghai Jiao Tong University, Shanghai Ninth People's Hospital
- SHShuying Huang
Shanghai Jiao Tong University, Shanghai Ninth People's Hospital
- XCXiaonan Chen
Shanghai Jiao Tong University, Shanghai Ninth People's Hospital
Topics & keywords
- KEAP1
- Hydrogen sulfide
- Doxorubicin
- Chemistry
- Glutathione
- GPX4
- Cell biology
- Cancer research