Regulation of nuclear calcium and ROS by Angiotensin II in heart cells. Régulation du calcium et ROS nucléaires par l'angiotensine II dans les cellules cardiaques.

我们实验室最近的工作使我们得出了我们的一般假设，即细胞核是细胞内的细胞。我们的早期工作开辟了一个新的领域，有助于更好地理解细胞生理学和生物学。这一新领域的进展，包括我们实验室的进展表明，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。后者被它们各自存在于细胞内的生物活性因子激活，如血管紧张素II （Ang II）。此外，我们最近的工作表明，作为一个细胞，细胞核确实具有核内结构，类似于细胞膜的结构，例如我们小组所称的核t管和核质网。所有这些核结构和膜蛋白与细胞膜的结构和膜蛋白一起工作，以满足细胞核的需要，从而使其在正常细胞功能的调节中发挥重要作用。此外，细胞核可以独立于其细胞活动，以提供实现其作用所需的因子。Ang II是一种循环活性章鱼肽，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，我们的工作表明，这些Ang II受体也存在于核膜中，并可能有助于心脏细胞收缩的调节和控制。这是通过细胞核对细胞质和细胞核钙水平的调节来完成的，钙水平负责心肌细胞收缩。钙水平也被认为与细胞的生死有关。此外，我们实验室最近发表的工作（由NSERC批准）表明，血管平滑肌细胞和心脏细胞的细胞膜和/或核膜Ang II受体的激活可诱导胞质和核氧化剂（ROS）的产生。然而，核膜Ang II受体的激活调节氧化应激的可能性，进而会或可能影响核钙和细胞功能，仍有待探索。***这个项目将帮助我们更好地了解Ang II在产生氧化应激和调节细胞质和细胞核Ca2+水平中的作用。众所周知，后一种离子水平调节心脏细胞收缩、心脏发育和衰老

Recent work from our laboratory led us to our general hypothesis that the nucleus is a cell within a cell. Our early work opened a new field that helped to better understand cell physiology and biology. The progress in this new field, including that of 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 latter are activated by their respective bioactive factors present inside the cells such as angiotensin II (Ang II). In addition, our recent work showed that, as a cell, the nucleus does possess intranuclear structures, similar to those of the cell membrane, such as those called by our group nuclear T-tubules and nucleoplasmic reticulum. All of these nuclear structures and membrane proteins work together with those of the cell membrane in order to supply the nucleus with its needs, thus enabling it to achieve its important role in the regulation of normal cell function. In addition, the nucleus can act independently of its cell to supply itself by the factors that are needed to achieve its role. Ang II, a circulating active octopeptide, 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 work showed that these Ang II receptors are also present in nuclear membranes and may contribute to the regulation and control of contraction of heart cells. This is done via the contribution of the nucleus to cytosolic and nuclear regulation of calcium level which is responsible for cardiac cell contraction. Calcium level is also known to be implicated in both the life and 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 Ang II receptors in vascular smooth muscle cells and heart cells induced generation of cytosolic and nuclear oxidants (ROS). However, the possibility that the activation of nuclear membranes Ang II receptors modulating oxidative stress, which in turn would or might affect nuclear calcium 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 latter ion is known to regulate heart cell contractions as well as heart development and aging.**