calpain and Blood-Platelet-Disorders

Topics: Blood Platelet Disorders; Blood Platelets; Calpain; Caspases; Dialysis; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Phosphatidylserines; Platelet Activation; Platelet Aggregation; Renal Dialysis; Thrombophilia; Thrombopoiesis; Uremia

Platelets from patients with Montreal platelet syndrome (MPS) consistently display a defect in the mechanisms that regulate platelet size during shape change and undergo spontaneous aggregation and stir-induced microaggregate formation. We now provide data that the surface glycoprotein composition of MPS platelets is indistinguishable from that of normal platelets. However, a defect in calcium-activated neutral proteinase (calpain) was detected in MPS platelets. The specific activity of calpain in the cytosolic fraction of platelets from four MPS patients was found to be only 30% of that in platelets from normal control donors (n = 18, P less than .001). Additionally, platelets from MPS patients (n = 3) contained only 50% (P less than .001) of the calpain I catalytic subunit antigen found in platelets from normal control donors (n = 9). Platelets from the asymptomatic father/grandfather of the MPS patients had normal amounts of both total calpain proteolytic activity and calpain I catalytic subunit antigen. This represents the first report of a defect in calpain in human cells. The abnormally low calpain activity in MPS platelets may account for the platelet defects characteristic of this disorder.

Topics: Blood Platelet Disorders; Blood Proteins; Calpain; Catalysis; Female; Humans; Hydrolysis; Immunoelectrophoresis, Two-Dimensional; Isoantigens; Male; Platelet Aggregation; Platelet Membrane Glycoproteins; Subcellular Fractions; Syndrome