自噬
心脏毒性
细胞生物学
基因敲除
阿霉素
下调和上调
信号转导衔接蛋白
细胞凋亡
癌症研究
化学
生物
信号转导
生物化学
基因
毒性
有机化学
化疗
遗传学
作者
Jihong Wang,Hong Yi,Juxiang Li,Yuting Yang,Sun Guo-fang,Yumei Xue,Ling He
出处
期刊:Life Sciences
[Elsevier]
日期:2024-08-13
卷期号:356: 122981-122981
标识
DOI:10.1016/j.lfs.2024.122981
摘要
Doxorubicin-induced cardiotoxicity (DIC) poses a significant challenge, impeding its widespread application. Emerging evidence suggests the involvement of ferroptosis in the DIC. While the downregulation of SLC7A11 expression has been linked to the promotion of ferroptosis, the precise regulatory mechanism remains unclear. Recent studies, including our own, have highlighted abnormal levels of autophagy adapter protein P62 and autophagy in DIC development. Thus, our study aimed to further investigate the role of autophagy and ferroptosis in DIC, elucidating underlying molecular mechanisms across molecular, cellular, and whole-organ levels utilizing gene knockdown, immunoprecipitation, and mass spectrometry techniques. The results of our findings unveiled cardiomyocyte damage, heightened autophagy levels, and ferroptosis in DOX-treated mouse hearts. Notably, inhibition of autophagy levels attenuated DOX-induced ferroptosis. Mechanistically, we discovered that the autophagy adaptor protein P62 mediates the entry of SLC7A11 into the autophagic pathway for degradation. Furthermore, the addition of autophagy inhibitors (CQ or BAF) could elevate SLC7A11 and GPX4 protein expression, reduce the accumulation of Fe
科研通智能强力驱动
Strongly Powered by AbleSci AI