Decreased thrombin affinity of cell-surface thrombomodulin following treatment of cultured endothelial cells with beta-D-xyloside.
Thrombomodulin, an endothelial cell-surface anticoagulant, has been postulated to contain a glycosaminoglycan. Thrombomodulin function was therefore studied in endothelial cells treated with beta-D-xyloside, an inhibitor of glycosaminoglycan attachment to proteoglycan core proteins. Beta-D-xyloside caused a reproducible 3 to 5-fold increase in the Km of thrombomodulin for thrombin and a 20-30% decrease in the rate of protein C activation by the thrombin-thrombomodulin complex. These results support a role for glycosaminoglycans in thrombomodulin function and suggest that beta-D-xylosides can be used to investigate both the anticoagulant mechanisms and the biosynthesis of cell-surface thrombomodulin.
Parkinson
J F
JF
Lilly Laboratories for Clinical Research, Indiana University, Indianapolis.
Garcia
J G
JG
Bang
N U
NU
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000502:physiology; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000494:pharmacology*; D011486:Protein C / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018179:Receptors, Thrombin; D013917:Thrombin / Q000378:metabolism*; D014468:Umbelliferones / Q000494:pharmacology*
D006025:Glycosaminoglycans; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D014468:Umbelliferones; D006923:Hymecromone; C014111:methylumbelliferyl-beta-D-xyloside; D013917:Thrombin