压力过载增加了GATA4通过内末林-1结合活性
N Hautala1, H Tokola, M Luodonpää
1Departments of Pharmacology and Toxicology and Physiology, Biocenter Oulu, University of Oulu, Finland.
Circulation
|February 7, 2001
概括
在压力过载期间,内末林-1 (ET-1) 迅速增加心肌细胞中的GATA4 DNA结合活性. 这种信号通路对于心脏中高变性生长和B型性尿素 (BNP) 基因调节至关重要.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 基因规则 基因规则
背景情况:
- 在血液动力过载期间控制心肌细胞缩的信号通路尚未完全理解.
- GATA4是一种心脏受限的转录因子,在心脏缩中调节像B型尿素 (BNP) 这样的基因.
研究的目的:
- 为了研究活体中应对压力过载时GATA转录因子激活的信号机制.
- 确定内甲素-1 (ET-1) 和血管新生素II在心脏压力过载期间调节GATA4活性中的作用.
主要方法:
- 在体内使用 arginine(8)-vasopressin (AVP) 诱导压力过载的老鼠模型.
- 凝移动转移试验分析转录因子与BNP促进体结合的分析.
- 使用内甲素-1受体对抗剂博森坦和 ангиотензин II 1 型受体对抗剂洛萨坦.
主要成果:
- 由AVP引起的压力过载增加了BNP和c-fosmRNA水平,但没有GATA4或GATA6mRNA.
- 压力过载在左心室显著增加了GATA4DNA结合活性.
- 博森坦,但不是洛萨坦,完全抑制了压力过载引起的GATA4结合活性增加.
结论:
- 内甲素-1 (ET-1) 作为一个信号分子,在应对压力过载时快速上调 GATA4 DNA 结合活性.
- 这种GATA4结合活性的快速上调是压力过载对心脏缩反应的一个关键事件.
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