Identification of the molecular basis of doxorubicin-induced cardiotoxicity

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

Research output: Contribution to journalArticle

683 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1639-1642
Number of pages4
JournalNature Medicine
Volume18
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

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Cardiac Myocytes
Doxorubicin
Type II DNA Topoisomerase
Reactive Oxygen Species
Organelle Biogenesis
Transcriptome
Oxidation-Reduction
Heart Failure
Cardiotoxicity
DNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Zhang, S., Liu, X., Bawa-Khalfe, T., Lu, L. S., Lyu, Y. L., Liu, L-F., & Yeh, E. T. H. (2012). Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature Medicine, 18(11), 1639-1642. https://doi.org/10.1038/nm.2919

Identification of the molecular basis of doxorubicin-induced cardiotoxicity. / Zhang, Sui; Liu, Xiaobing; Bawa-Khalfe, Tasneem; Lu, Long Sheng; Lyu, Yi Lisa; Liu, Leroy-Fong; Yeh, Edward T H.

In: Nature Medicine, Vol. 18, No. 11, 11.2012, p. 1639-1642.

Research output: Contribution to journalArticle

Zhang, S, Liu, X, Bawa-Khalfe, T, Lu, LS, Lyu, YL, Liu, L-F & Yeh, ETH 2012, 'Identification of the molecular basis of doxorubicin-induced cardiotoxicity', Nature Medicine, vol. 18, no. 11, pp. 1639-1642. https://doi.org/10.1038/nm.2919
Zhang, Sui ; Liu, Xiaobing ; Bawa-Khalfe, Tasneem ; Lu, Long Sheng ; Lyu, Yi Lisa ; Liu, Leroy-Fong ; Yeh, Edward T H. / Identification of the molecular basis of doxorubicin-induced cardiotoxicity. In: Nature Medicine. 2012 ; Vol. 18, No. 11. pp. 1639-1642.
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