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.

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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.