Identification of the molecular basis of doxorubicin-induced cardiotoxicity

被引：1476

作者：

Zhang, Sui ^{[1
]}

Liu, Xiaobing ^{[2
,3
]}

Bawa-Khalfe, Tasneem ^{[1
]}

Lu, Long-Sheng ^{[2
]}

Lyu, Yi Lisa ^{[4
]}

Liu, Leroy F. ^{[4
]}

Yeh, Edward T. H. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Cardiol, Houston, TX 77030 USA

[2] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA

[3] Shanghai Jiao Tong Univ, Dept Vasc Surg, Peoples Hosp 9, Sch Med, Shanghai 200030, Peoples R China

[4] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA

来源：

NATURE MEDICINE | 2012年 / 18卷 / 11期

基金：

美国国家卫生研究院;

关键词：

TOPOISOMERASE-II-BETA; INDUCED CARDIOMYOPATHY; HEART; GENE; TRANSCRIPTION; EXPRESSION; PREVENTION; PGC-1-BETA; APOPTOSIS; ADULT;

D O I：

10.1038/nm.2919

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-II beta) 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-II beta in cardiomyocytes.

引用

页码：1639 / +

页数：7

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