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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors.
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Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors.

机译:核前列腺素信号传导系统:通过七螺旋受体的生物发生和作用。

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摘要

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 E2-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.
机译:前列腺素是普遍存在的脂质介体,在心血管稳态,繁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)中起关键作用。这些脂质信使的作用机理被认为主要取决于它们与属于跨G蛋白偶联受体超家族的七螺旋跨膜的特定细胞表面受体的相互作用。越来越多的证据表明,这些受体可能共定位在细胞核上,在那里它们可以通过一系列生化事件来调节基因表达。在这种情况下,我们最近证明,前列腺素E2-EP3受体在脑微血管内皮细胞中显示出非典型的核区室化。对这些核EP3受体的刺激导致无细胞分离核系统中eNOS RNA的增加。这篇综述将强调这些发现并描述核前列腺素受体,特别是EP3受体如何通过鉴定位于该细胞器内的推测的转导元件如何影响基因表达,特别是eNOS。这些细胞内位点的脂质配体激活剂的潜在来源也将得到解决。位于核周包膜的G蛋白偶联受体的表达控制构成基因调节的一种新颖而独特的模式。

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