Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors
Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors
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DOI：
10.1139/y02-163
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发表时间：
2003-02-01
影响因子：
2.1
通讯作者：
Chemtob, S
中科院分区：
文献类型：
--
作者：
Gobeil, F;Vazquez-Tello, A;Chemtob, S
前列腺素是普遍存在的脂质介质，在心血管稳态、生殖和炎症以及许多重要的细胞过程（包括基因表达和细胞增殖）中发挥关键作用。这些脂质信使的作用机制被认为主要取决于它们与属于七螺旋跨膜G蛋白偶联受体超家族的特异性细胞表面受体的相互作用。越来越多的证据表明，这些受体可能共同定位于细胞核，在那里它们可以通过一系列生化事件调节基因表达。在这种情况下，我们最近已经证明，前列腺素E-2-EP 3受体在脑微血管内皮细胞中显示非典型的核区室化。这些核EP 3受体的刺激导致eNOS RNA在无细胞分离的核系统中的增加。这篇综述将强调这些发现，并描述如何核前列腺素受体，特别是EP 3受体，可能会影响基因表达，特别是eNOS，通过确定假定的转导元件位于这个细胞器。这些细胞内位点的脂质配体活化剂的潜在来源也将得到解决。位于核周膜的G蛋白偶联受体的表达控制构成了一种新颖而独特的基因调控模式。
Prostaglandins are ubiquitous lipid mediators that play pivotal roles in cardiovascular homeostasis, reproduction, and inflammation, as well as in many important cellular processes including gene expression and cell proliferation. The mechanism of action of these lipid messengers is thought to be primarily dependent on their interaction with specific cell surface receptors that belong to the heptahelical transmembrane spanning G protein-coupled receptor superfamily. Accumulating evidence suggests that these receptors may co-localize at the cell nucleus where they can modulate gene expression through a series of biochemical events. In this context, we have recently demonstrated that prostaglandin E-2-EP3 receptors display an atypical nuclear compartmentalization in cerebral microvascular endothelial cells. Stimulation of these nuclear EP3 receptors leads to an increase of eNOS RNA in a cell-free isolated nuclear system. This review will emphasize these findings and describe how nuclear prostaglandin receptors, notably EP3 receptors, may affect gene expression, specifically of eNOS, by identifying putative transducing elements located within this organelle. The potential sources of lipid ligand activators for these intracellular sites will also be addressed. The expressional control of G-protein-coupled receptors located at the perinuclear envelope constitutes a novel and distinctive mode of gene regulation.