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Updated: Aug 26, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Expression of p300 protects cardiac myocytes from apoptosis in vivo
Teruhisa Kawamura1, Koji Hasegawa, Tatsuya Morimoto
1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Abstract:
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.
Insights
Overexpressing p300 in the heart protects against doxorubicin-induced heart failure. This finding offers a potential therapeutic strategy for preserving cardiac function during chemotherapy.
Area of Science:
- Cardiology
- Molecular Biology
- Oncology
Background:
- Doxorubicin chemotherapy can cause cardiotoxicity by damaging heart cells.
- Doxorubicin reduces levels of p300, a protein crucial for maintaining heart cell function.
- The protective role of p300 against doxorubicin-induced heart damage is not well understood.
Purpose of the Study:
- To investigate the role of p300 in protecting heart cells from doxorubicin-induced apoptosis.
- To determine if increased p300 levels can prevent doxorubicin cardiotoxicity.
Main Methods:
- Used transgenic mice with increased heart p300 levels and wild-type mice.
- Administered doxorubicin to both groups of mice.
- Assessed survival rates, left ventricular function, cardiac gene expression, and apoptosis.
Main Results:
- Transgenic mice showed higher survival and better heart function compared to wild-type mice.
- Doxorubicin induced apoptosis in wild-type mice but not in transgenic mice.
- p300 overexpression increased cardiac bcl-2 and mdm-2 levels.
Conclusions:
- Overexpression of p300 protects heart cells from doxorubicin-induced apoptosis.
- Increased p300 levels mitigate acute heart failure in mice treated with doxorubicin.
