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Regulation of nuclear calcium and ros by angiotensin II in heart cells. régulation du calcium et ros nucléaires par l'angiotensione II dans les cellules cardiaques.

心脏细胞中血管紧张素 II 对核钙和 ROS 的调节。

基本信息

批准号：
227174-2011
负责人：
Bkaily, Ghassan
金额：
$ 2.19万
依托单位：
Université de Sherbrooke
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2013
资助国家：
加拿大
起止时间：
2013-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523927
关键词：
Regulation nuclear calcium ros angiotensin

项目摘要

Recent work from our laboratory showed that, similarly to a cell, the nucleus possesses membranes that contain proteins such as ionic channels, ionic transporters and G-protein coupled receptors (GPCRs). These later are activated by hormones and active circulating factors, such as angiotensin II (Ang II) and endothelin-1 (ET-1). All of these nuclear membranes proteins work together in order to supply the nucleus with its needs, thus enabling it to achieve its important role in the regulation of cell function. Ang II, a circulating active peptide, is known to affect the function of heart cells during embryonic development and growth. The receptor proteins known to be stimulated by this hormone are present in the cell membrane. However, our recent work showed that these Ang II as well as ET-1 receptors are also present in nuclear membranes and may regulate and control the intranuclear level of free Ca2+. This ion is known to be implicated in both the life and the death of the cell. Furthermore, our recent published work from our laboratory (was granted by NSERC) showed that activation of either cell membrane and/or nuclear membranes ET-1 receptors in vascular smooth muscle cells induced generation of nuclear ROS. However, the possibility that the activation of nuclear membranes Ang II receptors modulating ROS, which in turn would or might affect nuclear Ca2+ and cell function, remains to be explored.

我们实验室最近的工作表明，与细胞类似，细胞核具有含有蛋白质的膜，如离子通道，离子转运蛋白和G蛋白偶联受体（GPCR）。这些后来被激素和活性循环因子激活，如血管紧张素II（Ang II）和内皮素-1（ET-1）。所有这些核膜蛋白一起工作，以满足细胞核的需要，从而使其能够在调节细胞功能中发挥重要作用。血管紧张素II是一种循环活性肽，已知在胚胎发育和生长期间影响心脏细胞的功能。已知受这种激素刺激的受体蛋白存在于细胞膜中。然而，我们最近的工作表明，这些血管紧张素Ⅱ以及ET-1受体也存在于核膜，并可能调节和控制核内游离Ca ~（2+）的水平。已知该离子与细胞的生命和死亡有关。此外，我们实验室最近发表的工作（由NSERC授予）表明，血管平滑肌细胞中细胞膜和/或核膜ET-1受体的激活诱导核ROS的产生。然而，核膜Ang II受体的活化调节ROS，进而影响核Ca 2+和细胞功能的可能性仍有待探索。