Identification of the molecular basis of doxorubicin-induced cardiotoxicity

被引：1415

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

共 24 条

[1] Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-γ coactivator 1α
Arany, Zoltan
Novikov, Mikhail
Chin, Sherry
Ma, Yanhong
Rosenzweig, Anthony
Spiegelman, Bruce M.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (26) : 10086 - 10091
[2] Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells
Bawa-Khalfe, Tasneem
Cheng, Jinke
Wang, Zhengxin
Yeh, Edward T. H.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (52) : 37341 - 37349
[3] DIFFERENT PATTERNS OF GENE-EXPRESSION OF TOPOISOMERASE-II ISOFORMS IN DIFFERENTIATED TISSUES DURING MURINE DEVELOPMENT
CAPRANICO, G
TINELLI, S
AUSTIN, CA
FISHER, ML
ZUNINO, F
[J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1132 (01) : 43 - 48
[4] Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes
Force, Thomas
Kolaja, Kyle L.
[J]. NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (02) : 111 - 126
[5] Coordination of PGC-1β and iron uptake in mitochondrial biogenesis and osteoclast activation
Ishii, Kiyo-aki
Fumoto, Toshio
Iwai, Kazuhiro
Takeshita, Sunao
Ito, Masako
Shimohata, Nobuyuki
Aburatani, Hiroyuki
Taketani, Shigeru
Lelliott, Christopher J.
Vidal-Puig, Antonio
Ikeda, Kyoji
[J]. NATURE MEDICINE, 2009, 15 (03) : 259 - 266
[6] A topoisomerase IIβ-mediated dsDNA break required for regulated transcription
Ju, BG
Lunyak, VV
Perissi, V
Garcia-Bassets, I
Rose, DW
Glass, CK
Rosenfeld, MG
[J]. SCIENCE, 2006, 312 (5781) : 1798 - 1802
[7] Transcriptional coactivators PGC-1α and PGC-1β control overlapping programs required for perinatal maturation of the heart
Lai, Ling
Leone, Teresa C.
Zechner, Christoph
Schaeffer, Paul J.
Kelly, Sean M.
Flanagan, Daniel P.
Medeiros, Denis M.
Kovacs, Attila
Kelly, Daniel P.
[J]. GENES & DEVELOPMENT, 2008, 22 (14) : 1948 - 1961
[8] Liao Ronglih, 2007, V139, P251
[9] Topoisomerase IIβ-Mediated DNA double-strand breaks:: Implications in doxorubicin cardiotoxicity and prevention by dexrazoxane
Lyu, Yi Lisa
Kerrigan, John E.
Lin, Chao-Po
Azarova, Anna M.
Tsai, Yuan-Chin
Ban, Yi
Liu, Leroy F.
[J]. CANCER RESEARCH, 2007, 67 (18) : 8839 - 8846
[10] Role of topoisomerase IIβ in the expression of developmentally regulated genes
Lyu, Yi Lisa
Lin, Chao-Po
Azarova, Anna M.
Cai, Li
Wang, James C.
Liu, Leroy F.
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (21) : 7929 - 7941

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