Expression of p300 protects cardiac myocytes from apoptosis in vivo
Expression of p300 protects cardiac myocytes from apoptosis in vivo
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DOI：
10.1016/j.bbrc.2004.01.105
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发表时间：
2004-03-12
影响因子：
3.1
通讯作者：
Kita, T
中科院分区：
文献类型：
--
作者：
Kawamura, T;Hasegawa, K;Kita, T
阿霉素是一种抑制心脏特异性基因表达并诱导心肌细胞凋亡的抗肿瘤药物。阿霉素消耗心脏p300，一种维持心肌细胞分化表型所需的转录辅激活因子。然而，p300在保护阿霉素诱导的细胞凋亡中的作用尚不清楚。对心脏中过表达p300的转基因小鼠和野生型小鼠进行多柔比星治疗。与野生型小鼠相比，转基因小鼠表现出更高的存活率以及更好的左心室功能和心肌α-肌节肌动蛋白表达。阿霉素在野生型小鼠中诱导心肌细胞凋亡，但在转基因小鼠中不诱导。p300的表达增加了心脏bcl-2和mdm-2的水平，但不增加p53或bcl-2家族的其他成员的水平。这些结果表明，p300的过度表达保护心肌细胞从阿霉素诱导的凋亡，并减少在体内的成年小鼠急性心力衰竭的程度。(C)2004年爱思唯尔公司All rights reserved.
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. (C) 2004 Elsevier Inc. All rights reserved.