...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity
【24h】

Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity

机译：GATA-4在细胞存活和药物诱导的心脏毒性中的重要作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In recent years, significant progress has been made in understanding cardiomyocyte differentiation. However, little is known about the regulation of myocyte survival despite the fact that myocyte apoptosis is a leading cause of heart failure. Here we report that transcription factor GATA-4 is a survival factor for differentiated, postnatal cardiomyocytes and an upstream activator of the antiapoptotic gene Bcl-X. An early event in the cardiotoxic effect of the antitumor drug doxorubicin is GATA-4 depletion, which in turn causes cardionnyocyte apoptosis. Mouse heterozygotes for a null Gata4 allele have enhanced susceptibility to doxorubicin cardiotoxicity. Genetic or pharmacologic enhancement of GATA-4 prevents cardionnyocyte apoptosis and drug-induced cardiotoxicity. The results indicate that GATA-4 is an antiapoptotic factor required for the adaptive stress response of the adult heart. Modulation of survival/apoptosis genes by tissue-specific transcription factors may be a general paradigm that can be exploited effectively for cell-specific regulation of apoptosis in disease states.
机译：近年来，在了解心肌细胞分化方面已取得重大进展。然而，尽管肌细胞凋亡是心力衰竭的主要原因，但对肌细胞存活的调控知之甚少。在这里我们报告转录因子GATA-4是分化的，出生后的心肌细胞的生存因子和抗凋亡基因Bcl-X的上游激活剂。抗肿瘤药物阿霉素的心脏毒性作用中的一个早期事件是GATA-4耗竭，这反过来又导致心肌细胞凋亡。无效的Gata4等位基因的小鼠杂合子对阿霉素心脏毒性的敏感性增强。 GATA-4的遗传或药理作用增强可防止心肌细胞凋亡和药物诱导的心脏毒性。结果表明，GATA-4是成年心脏适应性应激反应所需的抗凋亡因子。组织特异性转录因子对存活/凋亡基因的调控可能是一种普遍的范例，可以有效地用于疾病状态下细胞凋亡的细胞特异性调控。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号