Red blood cells are an integral part of the cardiovascular system carrying oxygen to the tissues. These red cells normally survive in circulation for only about 120 days at which time they are removed and destroyed. Although many changes occur as young cells become """"""""old"""""""" the cause of these changes has not been identified although most, if not all, could be mediated by increased cellular calcium. We propose to determine whether cellular oxidation and the resulting complexes between oxidation products, particularly hemoglobin, and cytoplasmically accessible cell membrane proteins may be responsible for initiating red cell senescence through increases in intracellular calcium. We further intend to determine the mechanisms by which the increase in free ionic cell calcium is accomplished. Our immediate goal is to understand the mechanism of cell aging with the ultimate goal of improving the survival of banked red cells through deceleration or arrest of the red cell aging process. Cellular oxidation will be accomplished by treating isolated normal human erythrocytes with low concentrations of specific peroxides for short periods of time. Cytosolic free calcium will be measured in peroxide treated and control cells under various experimental conditions using 19F - NMR spectroscopy of the intra-cellular calcium chelator compound BAPTA.
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