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.

我们实验室最近的工作表明，与细胞相似，细胞核具有包含离子通道，离子转运体和g蛋白偶联受体（gpcr）等蛋白质的膜。这些后期被激素和活跃的循环因子激活，如血管紧张素II （Ang II）和内皮素-1 （ET-1）。所有这些核膜蛋白协同工作，以满足细胞核的需要，从而使其在调节细胞功能方面发挥重要作用。Ang II是一种循环活性肽，已知在胚胎发育和生长过程中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Ang II以及ET-1受体也存在于核膜中，并可能调节和控制核内游离Ca2+的水平。已知这种离子与细胞的生与死都有关系。此外，我们实验室最近发表的工作（由NSERC批准）表明，血管平滑肌细胞中细胞膜和/或核膜ET-1受体的激活诱导了核ROS的产生。然而，核膜Ang II受体激活调节ROS的可能性，进而会或可能影响核Ca2+和细胞功能，仍有待探索。

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. This project will help us to better understand the role of Ang II in generating oxidative stress and regulating the level of both cytosolic and nuclear Ca2+. The level of this later ion is known to regulate heart cell contractions as well.