The Imbalance of p53-Park7 Signaling Axis Induces Iron Homeostasis Dysfunction in Doxorubicin-Challenged Cardiomyocytes.

ABSTRACT: Doxorubicin (DOX)-induced cardiotoxicity (DoIC) is a major side effect for cancer patients. Recently, ferroptosis, triggered by iron overload, is demonstrated to play a role in DoIC. How iron homeostasis is dysregulated in DoIC remains to be elucidated. Here, the authors demonstrate that DOX challenge exhibits reduced contractile function and induction of ferroptosis-related phenotype in cardiomyocytes, evidenced by iron overload, lipid peroxide accumulation, and mitochondrial dysfunction. Compared to Ferric ammonium citrate (FAC) induced secondary iron overload, DOX-challenged cardiomyocytes show a dysfunction of iron homeostasis, with decreased cytoplasmic and mitochondrial iron-sulfur (FeS) cluster-mediated aconitase activity and abnormal expression of iron homeostasis-related proteins

SUBMITTER: Pan J 

PROVIDER: S-EPMC10214246 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature