| First Author | Zhang S | Year | 2012 |
| Journal | Nat Med | Volume | 18 |
| Issue | 11 | Pages | 1639-42 |
| PubMed ID | 23104132 | Mgi Jnum | J:273153 |
| Mgi Id | MGI:6283921 | Doi | 10.1038/nm.2919 |
| Citation | Zhang S, et al. (2012) Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 18(11):1639-42 |
| abstractText | 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-IIbeta) 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-IIbeta in cardiomyocytes. |
