Vascular cell signaling by membrane estrogen receptors
Vascular cell signaling by membrane estrogen receptors
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DOI：
10.1016/j.steroids.2008.01.008
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发表时间：
2008-10-01
期刊：
影响因子：
2.7
通讯作者：
Bender, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Kim, Kyuny Hee;Moriarty, Katie;Bender, Jeffrey R.
雌激素作用的定义已经从转录调节扩展到许多信号转导级联的快速、膜启动激活。雌激素的多种生物学效应已在许多动物、细胞和分子研究中显示，这支持雌激素对血管结构、功能和细胞信号传导的有利作用。几个实验室的工作表明，这些作用是由不同形式的雌激素受体（ER）a介导的。这包括雌激素刺激的内皮型一氧化氮合酶（eNOS）的快速激活，导致动脉粥样硬化保护，血管生成促进产物一氧化氮（NO）的产生。我们已经描述了ER 46（ER α的N-末端截短亚型）在人内皮细胞（EC）中的表达及其在膜启动的对17 β-雌二醇（E2）的快速反应中的关键作用。我们提出了一个ER 46为中心的，eNOS激活分子复合物在人类EC小窝膜，包含c-Src，磷脂酰肌醇3-激酶（PI 3 K），Akt和eNOS。我们先前的研究支持雌激素通过c-Src/PI 3 K/Akt级联反应诱导EC中eNOS的快速激活。在这篇综述中，我们描述了雌激素诱导的，快速的，非基因组的行动在内皮细胞，驱动c-Src-ER 46-小窝蛋白-1相互作用，随之而来的激活eNOS。在激素替代疗法的持续争议中，这些分子和细胞数据，定义了对内皮细胞有利的雌激素效应，为解决这些临床问题提供了强大的动力。(C)2008年爱思唯尔公司All rights reserved.
The definition of estrogen's actions has expanded from transcriptional regulation to the rapid, membrane-initiated activation of numerous signal transduction cascades. Multiple biological effects of estrogen have been shown in numerous animals, cellular and molecular studies, which support the favorable effects of estrogen on vascular structure, function, and cell signaling. Work from several laboratories has shown that these effects are mediated by distinct forms of estrogen receptor (ER) a. This includes estrogen-stimulated rapid activation of endothelial nitric oxide synthase (eNOS), resulting in the elaboration of the athero-protective, angiogenesis-promoting product nitric oxide (NO). We have described the expression of ER46, an N-terminus truncated isoform of the ER alpha, in human endothelial cells (EC), and its critical role in membrane-initiated, rapid responses to 17 beta-estradiol (E2). We have proposed an ER46-centered, eNOS activating molecular complex in human EC caveolar membranes, containing c-Src, phosphatidylinositol 3-kinase (PI3K), Akt and eNOS. Our previous studies support estrogen-induced rapid eNOS activation via a sequential c-Src/PI3K/Akt cascade in EC. In this review, we describe estrogen-induced, rapid, non-genomic actions in endothelium, driven by c-Src-ER46-caveolin-1 interactions, with consequent activation of eNOS. Amidst ongoing controversies in hormone replacement therapy, these molecular and cellular data, defining favorable estrogenic effects on the endothelium, provide a strong impetus to resolve these clinical questions. (C) 2008 Elsevier Inc. All rights reserved.