Plasma Membrane Redox System During Aging and Caloric Restriction





R de Cabo1, C Gilman2, M Garcia3, G Lopez3, M Mattson2, M Anson1, P Navas3 and Mark A. Lane1

1Nutritional and Molecular Physiology Unit, Laboratory of Neurosciences, NIA, NIH, 5600 Nathan Shock dr. Baltimore MD-21224 2Laboratory of Neurosciences NIA, NIH 3Universidad Pablo de Olavide, Seville, Spain



Reactive oxygen species (ROS) are generated following ligand-receptor interactions and they are involved as highly specific second messengers in signaling cascades regulating cell proliferation and differentiation. ROS are continuously generated intracellularly by several sources, especially in mitochondria, the primary sources of ROS involved in receptor-mediated signaling cascades are at the plasma membrane. The ROS generators are typically NAD(P)H oxidases with rapid kinetics of activation and inactivation. This quick kinetics leads to quick up- and downregulation of intracellular ROS production within the short time required for the transduction of signals from the plasma membrane to the nucleus. The production of ROS at the plasma membrane is tightly linked to the redox-activation of protein kinases, protein phosphatases, and transcription factors. Furthermore, ROS act in concert with intracellular Ca2+ in signaling pathways, which regulate the balance of cell proliferation versus cell cycle arrest and cell death. The delicate intracellular interplay between oxidizing and reducing equivalents allows ROS to function as second messengers in the control of cell proliferation, differentiation and apoptosis. A reduction in energy intake by caloric restriction, has been shown to decrease the intracellular accumulation of ROS and an increase life span. Can calorie restriction induce a low level production of ROS (non-damaging), which will enhance signaling processes through the plasma membrane redox system? We studied free radical production and activities of plasma membrane associated oxidoreductases in liver plasma membranes isolated from caloric restricted mice and rats and cells in culture.




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