Inhibition of protein cross-linking in Ca2+-enriched human erythrocytes and activated platelets.
Treatment of human erythrocytes with Ca2+, in the presence of ionophore A23187, causes the formation of high molecular weight (greater than 10(6)) membrane protein polymers. This phenomenon, known to involve cross-linking of essentially all of the band 4.1 and 2.1 (ankyrin) proteins, as well as some spectrin, band 3, and hemoglobin molecules, could be prevented by preincubating the cells with a noncompetitive inhibitor of intrinsic transglutaminase, 2-[3-(diallylamino)propionyl]benzothiophene, at concentrations of about (3-6) X 10(-4) M. The compound also eliminated the proteolytic breakdown of the two major transmembrane proteins band 3 and glycophorin, which would otherwise occur during the Ca2+ loading of fresh human red cells. In addition, the inhibitor effectively blocked the formation of a cross-linked protein polymer in thrombin-activated human platelets.
D001792:Blood Platelets / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000097:blood*; D010974:Platelet Aggregation; D013876:Thiophenes / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology; D011503:Transglutaminases / Q000037:antagonists & inhibitors
D046911:Macromolecular Substances; D008565:Membrane Proteins; D013876:Thiophenes; D000001:Calcimycin; C051179:2-(3-(diallylamino)propionyl)benzothiophene; D011503:Transglutaminases; D013917:Thrombin; D002118:Calcium