AT1 Receptor Regulation
AT1 Receptor Regulation
复制标题
AT1受体调节
DOI：
--
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
G. Nickenig
中科院分区：
文献类型：
--
作者：
S. Wassmann;G. Nickenig
临床和实验研究表明，AT1受体的表达和调控在动脉粥样硬化、高血压等心血管疾病的发病机制中起着重要作用。AT1受体的表达水平决定了血管紧张素II的生物学功效。许多激动剂，如血管紧张素II、生长因子、低密度脂蛋白胆固醇、胰岛素、雌激素、黄体酮、活性氧、细胞因子、一氧化氮等，都可以调节AT1受体的表达。AT1受体的调节机制包括受体内化、脱敏、受体前mrna的选择性剪接，最重要的是通过转录和转录后机制调节其基因表达。转录后机制主导着AT1受体的调控。rna结合蛋白与AT1受体mRNA的5 ‘和3 ’非翻译区结合已被证明参与mRNA稳定性的调节。最近的研究表明，AT1受体mRNA的poly-A尾部附近的一个区域具有二级结构，形成茎环，对蛋白质-mRNA相互作用很重要。第一个确定的AT1受体结合蛋白是钙网蛋白，如果被磷酸化，它会结合AT1受体mRNA的同源序列并导致mRNA的不稳定。信号转导分子如cAMP、活性氧、MAP激酶、一氧化氮、PI-3激酶等已被证明参与几种激动剂对AT1受体的调节。AT1受体表达失调的病理生理相关性已在许多体外、体内和人体研究中得到证实。高胆固醇血症、雌激素缺乏和高胰岛素血症与AT1受体表达增强和氧化应激增加有关，AT1受体拮抗剂抑制病理细胞过程和内皮功能障碍和动脉粥样硬化病变的发展。AT1受体过表达很可能是一种潜在的分子机制，将外源性风险因素与慢性血管疾病的细胞事件联系起来。
Clinical and experimental studies have demonstrated that AT1 receptor expression and regulation play an important role in the pathogenesis of cardiovascular diseases such as atherosclerosis and hypertension. The expression levels of the AT1 receptor define the biological efficacy of angiotensin II. Many agonists, as for example angiotensin II, growth factors, low-density lipoprotein cholesterol, insulin, estrogen, progesterone, reactive oxygen species, cytokines, nitric oxide, and many others are known to regulate AT1 receptor expression. Mechanisms of AT1 receptor regulation include receptor internalization, desensitization, alternative splicing of receptor pre-mRNA, and most importantly modulation of its gene expression by transcriptional and posttranscriptional mechanisms. Posttranscriptional mechanisms predominate AT1 receptor regulation. Binding of RNA-binding proteins to the 5′ and 3′ untranslated region of the AT1 receptor mRNA has been shown to be involved in the regulation of mRNA stability. Recent studies revealed that a region just adjacent to the poly-A tail of the AT1 receptor mRNA, which has a secondary structure that forms a stem loop, is important for the protein-mRNA interaction. The first identified AT1 receptor binding protein is calreticulin, which, if phosphorylated, binds to this cognate sequence of the AT1 receptor mRNA and leads to mRNA destabilization. Signal transduction molecules such as cAMP, reactive oxygen species, MAP kinases, nitric oxide, PI-3 kinase, and others have been shown to be involved in AT1 receptor regulation by several agonists. The pathophysiological relevance of dysregulated AT1 receptor expression has been demonstrated in many in vitro, in vivo and human studies. Hypercholesterolemia, estrogen deficiency, and hyperinsulinemia are associated with enhanced AT1 receptor expression and increased oxidative stress, and AT1 receptor antagonism inhibits pathological cellular processes and the development of endothelial dysfunction and atherosclerotic lesions. AT1 receptor overexpression very likely represents, among other things, a potential molecular mechanism that links exogenous risk factors to cellular events in chronic vascular disease.
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血管平滑肌 I 型血管紧张素 II 受体 mRNA 因环 AMP 升高剂而不稳定。
影响因子：
3.6
作者：
Wang,X;Nickenig,G;Murphy,TJ
通讯作者：
Murphy,TJ
雌激素通过与受体 mRNA 5 前导序列结合的胞质蛋白调节血管紧张素 AT1 受体的表达。
DOI：
10.1210/endo.140.11.7242
发表时间：
1999
期刊：
Endocrinology.
影响因子：
--
作者：
Krishnamurthi,K;Verbalis,JG;Zheng,W;Wu,Z;Clerch,LB;Sandberg,K
通讯作者：
Sandberg,K
大鼠 1 型血管紧张素 II 受体 mRNA 水平的组织特异性调节。
DOI：
10.1161/01.hyp.28.3.403
发表时间：
1996
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Sechi,LA;Griffin,CA;Giacchetti,G;Valentin,JP;Llorens-Cortes,C;Corvol,P;Schambelan,M
通讯作者：
Schambelan,M
影响因子：
3.6
作者：
B. Lassègue;R. Alexander;G. Nickenig;M. Clark;T. Murphy;K. Griendling
通讯作者：
B. Lassègue;R. Alexander;G. Nickenig;M. Clark;T. Murphy;K. Griendling
通过表达蛋白激酶抑制剂/增强型绿色荧光融合蛋白来抑制环 AMP 依赖性激酶，可减弱血管平滑肌细胞中血管紧张素 II 诱导的 1 型 AT1 受体 mRNA 下调。
影响因子：
3.6
作者：
Wang,X;Murphy,TJ
通讯作者：
Murphy,TJ