Modulation of angiotensin II signaling for GATA4 activation by homocysteine.
Modulation of angiotensin II signaling for GATA4 activation by homocysteine.
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高半胱氨酸调节血管紧张素 II 信号传导以激活 GATA4。
DOI：
10.1089/ars.1999.1.2-233
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发表时间：
1999
影响因子：
6.6
通讯作者：
Jeffrey B. Blumberg
中科院分区：
文献类型：
--
作者：
Yuichiro J. Suzuki;S. Shi;Jeffrey B. Blumberg
同型半胱氨酸（Hcy）是一种氧化还原活性含硫醇化合物，在心血管系统中具有促氧化和致病特性。血管紧张素II （Ang II）在与年龄相关的心血管疾病中也起着重要作用。最近，GATA4转录因子被认为是心力衰竭的中介。我们研究了这些元素在NIH/3T3成纤维细胞中的相互关系，发现Ang II诱导GATA4活性，Hcy改变Ang II信号传导。电泳迁移率转移测定确定用Ang II处理细胞诱导DNA结合活性到GATA一致序列。这种激活是短暂的，在30分钟时达到峰值。Supershift分析显示GATA结合蛋白为GATA4。Ang II也以类似的动力学诱导NFAT活性。Hcy预处理细胞（100微米）将Ang ii诱导的NFAT和GATA激活的峰值延迟至60分钟。Ang ii介导的c-fos血清反应因子（SRF）的激活同样被Hcy延迟。这些结果表明，Hcy作用的致病机制可能部分通过调节基因转录的Ang ii信号传导介导。
Homocysteine (Hcy) is a redox active thiol-containing compound with pro-oxidant and pathogenic properties in the cardiovascular system. Angiotensin II (Ang II) also plays important roles in age-associated cardiovascular disease. Recently, the GATA4 transcription factor was recognized as a mediator of heart failure. We investigated the interrelationship of these elements in NIH/3T3 fibroblasts and found that Ang II induces GATA4 activity and Hcy alters Ang II signaling. Electrophoretic mobility shift assays determined that treatment of cells with Ang II induced DNA binding activity to the GATA consensus sequence. This activation was transient with a peak occurring at 30 min. Supershift analysis revealed the GATA binding protein as GATA4. Ang II also induced NFAT activity with similar kinetics. Pretreatment of cells with Hcy (100 microM) delayed the peak of Ang II-induced NFAT and GATA activation to 60 min. Ang II-mediated activation of c-fos serum response factor (SRF) was similarly delayed by Hcy. These results suggest the pathogenic mechanism of Hcy action may be mediated in part via modulation of Ang II-signaling for gene transcription.
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影响因子：
20.1
作者：
GRIENDLING, KK;MINIERI, CA;ALEXANDER, RW
通讯作者：
ALEXANDER, RW
影响因子：
158.5
作者：
SELHUB, J;JACQUES, PF;ROSENBERG, IH
通讯作者：
ROSENBERG, IH
生物硫醇对 DNA-蛋白质相互作用的氧化还原调节。
影响因子：
--
作者：
Suzuki,YJ;Packer,L
通讯作者：
Packer,L
影响因子：
15.9
作者：
STARKEBAUM, G;HARLAN, JM
通讯作者：
HARLAN, JM
DOI：
10.1073/pnas.94.14.7543
发表时间：
1997-07-08
影响因子：
11.1
作者：
Herzig, TC;Jobe, SM;Markham, BE
通讯作者：
Markham, BE