HUMAN ANGIOTENSIN II RECEPTOR GENE REGULATION

描述：高血压，一个主要的公共卫生问题， 超过15%的人口，是最重要的风险因素， 心血管疾病是心力衰竭、肾衰竭和 中风 由于肾素-血管紧张素系统（RAS）在血管紧张素转化中起着重要作用， 盐和水的体内平衡和维持血管张力， 该系统的组成部分代表了一个潜在的候选人的病因学 高血压 该提案将重点关注血管紧张素II（Ang II） 受体，RAS的组成部分，因为这些细胞表面受体是 负责介导血管紧张素II的生理作用。 近日有 表明Ang 11与两种不同的细胞因子相互作用， 血管紧张素II受体的亚型，AT 1和AT 2。 的完整特征 AT 1和AT 2受体的结构和生化特性， 他们的基因对于充分理解调控基因是必不可少的。 血管紧张素Ⅱ的作用和这些受体在血管紧张素Ⅱ受体的潜在作用。 高血压以及其他心血管疾病的发病机制。 目前，对人AT 1和AT 2受体（hAT 1 R）的了解很少 和hAT 2 R）基因或它们是如何转录调控的，以及为什么 合成多个可变剪接的mRNA转录物。 此外，关于其功能或信号转导， hAT 2 R的机制。 因此，本项目的长期目标 是为了表征hAT 1 R和hAT 2 R基因，并研究hAT 1 R和hAT 2 R基因的表达。 调节这些基因表达的分子机制， 表征hAT 2 R的生物化学性质。 本提案的具体目标是：1）定义顺式调节 参与选择性指导hAT 1 R转录的机制 和hAT 2 R基因的表达; 2）检测 假设四种不同的hAT 1 R mRNA差异表达， 3)检验四种不同的hAT 1 R mRNA转录本是 在体外和体内以不同的效率翻译，4）测试 具有外显子3 hAT 1 R mRNA编码新的hAT 1 R的假设，和5） 利用酵母双杂交系统研究hAT 2 R信号转导 机制。

DESCRIPTION: Hypertension, a major public health problem afflicting more than 15% of the population, is the most significant risk factor in cardiovascular disease and major cause of heart failure, kidney failure and stroke. Since the renin-angiotensin system (RAS) plays a central role in salt and water homeostasis and the maintenance of vascular tone, each component of this system represents a potential candidate in the etiology of hypertension. This proposal will focus on the angiotensin II (Ang II) receptor, a component of the RAS, since these cell-surface receptors are responsible for mediating Ang II physiological effects. Recently, it was demonstrated that Ang 11 interacts with two pharmacologically distinct subtypes of Ang II receptors, AT1 and AT2. The complete characterization of the structural and biochemical properties of the AT1 and AT2 receptors and their genes is essential for the full understanding of the regulatory actions of Ang II and the potential role of these receptors in the pathogenesis of hypertension as well as other cardiovascular disorders. Currently, very little is known about the human AT1 and AT2 receptors (hAT1R and hAT2R) genes or how they are transcriptionally regulated and why multiple alternatively spliced mRNA transcripts are synthesized. Furthermore, little is known about the function or the signal transduction mechanism(s) of the hAT2R. Therefore, the long term goals of this project are to characterize the hAT1R and hAT2R genes and to investigate the molecular mechanisms that regulate the expression of these genes and to characterize the biochemical properties of the hAT2R. The specific aims of this proposal are to: 1) Define the cis-regulatory mechanisms involved in selectively directing the transcription of the hAT1R and hAT2R genes by utilizing DNA-mediated gene transfer, 2) Test the hypothesis that the four distinct hAT1R mRNAs are differentially expressed, 3) Test the hypothesis that the four distinct hAT1R mRNA transcripts are translated with differential efficiencies in vitro and in vivo, 4) Test the hypothesis that hAT1R mRNAs which harbor exon 3 encode a novel hAT1R, and 5) Utilize the yeast two-hybrid system to investigate hAT2R signal transduction mechanism(s).