Preserved function of the plasma membrane calcium pump of red blood cells from diabetic subjects with high levels of glycated haemoglobin

The activity of the plasma membrane Ca2+-pump decreases steeply throughout the 120 days lifespan of normal human red blood cells. Experiments with isolated membrane preparations showed that glycation of a lysine residue near the catalytic site of the pump ATPase had a powerful inhibitory effect. This prompted the question of whether glycation is the mechanism of age-related decline in pump activity in vivo. It is important to investigate this mechanism because the Ca2+ pump is a major regulator of Ca2+ homeostasis in all cells. Its impaired activity in diabetic patients, continuously exposed to high glycation rates, may thus contribute to varied tissue pathology in this disease. We measured Ca2+-pump activity as a function of red cell age in red cells from diabetics continuously exposed to high glucose concentrations, as documented by their high mean levels of glycated haemoglobin. The distribution of Ca2+-pump activities was indistinguishable from that in non-diabetics, and the pattern of activity decline with cell age in the diabetics’ red cells was identical to that observed in red cells from non-diabetics. These results indicate that in intact cells the Ca2+ pump is protected from glycation-induced inactivation.