| First Author | Kawamura T | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 315 |
| Issue | 3 | Pages | 733-8 |
| PubMed ID | 14975762 | Mgi Jnum | J:110550 |
| Mgi Id | MGI:3640610 | Doi | 10.1016/j.bbrc.2004.01.105 |
| Citation | Kawamura T, et al. (2004) Expression of p300 protects cardiac myocytes from apoptosis in vivo. Biochem Biophys Res Commun 315(3):733-8 |
| abstractText | Doxorubicin is an anti-tumor agent that represses cardiac-specific gene expression and induces myocardial cell apoptosis. Doxorubicin depletes cardiac p300, a transcriptional coactivator that is required for the maintenance of the differentiated phenotype of cardiac myocytes. However, the role of p300 in protection against doxorubicin-induced apoptosis is unknown. Transgenic mice overexpressing p300 in the heart and wild-type mice were subjected to doxorubicin treatment. Compared with wild-type mice, transgenic mice exhibited higher survival rate as well as more preserved left ventricular function and cardiac expression of alpha-sarcomeric actin. Doxorubicin induced myocardial cell apoptosis in wild-type mice but not in transgenic mice. Expression of p300 increased the cardiac level of bcl-2 and mdm-2, but not that of p53 or other members of the bcl-2 family. These findings demonstrate that overexpression of p300 protects cardiac myocytes from doxorubicin-induced apoptosis and reduces the extent of acute heart failure in adult mice in vivo. |
