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 Ca(2+)-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 Ca(2+) pump is a major regulator of Ca(2+) 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 Ca(2+)-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 Ca(2+)-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 Ca(2+) pump is protected from glycation-induced inactivation.
Bookchin
Robert M
RM
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Etzion
Zipora
Z
Lew
Virgilio L
VL
Tiffert
Teresa
T
D003920:Diabetes Mellitus / Q000097:blood* / Q000201:enzymology*; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D013997:Time Factors
D006442:Glycated Hemoglobin; D053499:Plasma Membrane Calcium-Transporting ATPases