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. 2012 Nov;18(11):1639-42.
doi: 10.1038/nm.2919. Epub 2012 Oct 28.

Identification of the molecular basis of doxorubicin-induced cardiotoxicity

Sui Zhang  1 , Xiaobing Liu, Tasneem Bawa-Khalfe, Long-Sheng Lu, Yi Lisa Lyu, Leroy F Liu, Edward T H Yeh
Affiliations

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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