Identification of the molecular basis of doxorubicin-induced cardiotoxicity - PubMed

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• PMID: 23104132
• DOI: 10.1038/nm.2919

Identification of the molecular basis of doxorubicin-induced cardiotoxicity

Sui Zhang et al. Nat Med. 2012 Nov.

Abstract

Doxorubicin is believed to cause dose-dependent cardiotoxicity through redox cycling and the generation of reactive oxygen species (ROS). Here we show that cardiomyocyte-specific deletion of Top2b (encoding topoisomerase-IIβ) protects cardiomyocytes from doxorubicin-induced DNA double-strand breaks and transcriptome changes that are responsible for defective mitochondrial biogenesis and ROS formation. Furthermore, cardiomyocyte-specific deletion of Top2b protects mice from the development of doxorubicin-induced progressive heart failure, suggesting that doxorubicin-induced cardiotoxicity is mediated by topoisomerase-IIβ in cardiomyocytes.

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