钠钙交换体NCX1在心脏中的表达依赖于GATA因子。
Cardiac expression of the Na(+)/Ca(2+) exchanger NCX1 is GATA factor dependent.
作者信息
Nicholas S B, Philipson K D
机构信息
Departments of Physiology and Medicine and the Cardiovascular Research Laboratories, University of California, Los Angeles, School of Medicine, Los Angeles, California 90095-1760, USA.
出版信息
Am J Physiol. 1999 Jul;277(1):H324-30. doi: 10.1152/ajpheart.1999.277.1.H324.
The cardiac sarcolemmal Na(+)/Ca(2+) exchanger plays a primary role in Ca(2+) efflux and is important in regulating intracellular Ca(2+) and beat-to-beat contractility. Of the three Na(+)/Ca(2+) exchanger genes cloned (NCX1, NCX2, and NCX3), only NCX1 is expressed in cardiac myocytes. NCX1 has alternative promoters for heart, kidney, and brain tissue-specific transcripts. Analysis of the cardiac NCX1 promoter (at -336 bp) identified a cardiac-specific minimum promoter (at -137) and two GATA sites (at -75 and -145). In this study, gel shift and supershift analyses identified GATA-4 in primary neonatal cardiac myocytes. Site-directed mutagenesis of the GATA-4 site at -75 abolishes binding and reduces activity of the minimum and full-length promoters by >90 and approximately 60%, respectively. Mutation of the GATA site at -145 reduces activity of the full-length promoter by approximately 30%. Mutation of an E-box at -175 does not alter promoter activity.
心肌肌膜钠/钙交换器在钙离子外流中起主要作用，对调节细胞内钙离子及逐搏收缩性很重要。在已克隆的三个钠/钙交换器基因（NCX1、NCX2和NCX3）中，只有NCX1在心肌细胞中表达。NCX1具有用于心脏、肾脏和脑组织特异性转录本的可变启动子。对心脏NCX1启动子（-336 bp处）的分析确定了一个心脏特异性最小启动子（-137处）和两个GATA位点（-75和-145处）。在本研究中，凝胶迁移和超迁移分析在原代新生心肌细胞中鉴定出GATA-4。-75处GATA-4位点的定点诱变消除了结合，并使最小启动子和全长启动子的活性分别降低>90%和约60%。-145处GATA位点的突变使全长启动子的活性降低约30%。-175处E盒的突变不改变启动子活性。
Zotero 插件