Interaction of fucoidan with proteases and inhibitors of coagulation and fibrinolysis.
The interactions of fucoidan with glutamic plasminogen (Glu-Plg), two-chain tissue plasminogen activator (t-PA), LMwt-urokinase, thrombin, and antithrombin III (AT-III) were investigated using fucoidan-sepharose affinity chromatography. The results showed 1) a high degree of affinity between fucoidan-sepharose and Glu-Plg; Lmwt-urokinase and thrombin while t-Pa and AT-III did not bind with fucoidan-sepharose. 2) The double reciprocal plot for the LMwt-urokinase activation of Glu-Plg showed that plasminogen activator inhibitor (PAI-1) inhibited this reaction in a noncompetitive manner and that the presence of fucoidan decreased Km for this interaction by 50% and increased Kcat by 30-fold, 3) The double reciprocal plot for the t-PA activation of Glu-Plg showed that PAI-1 inhibited this reaction in a competitive manner and that fucoidan in conjunction with 6-aminohexanoic acid (6-AH) increased Kcat for this interaction by 5-fold without affecting Km. 4) Fucoidan enhanced the interaction of thrombin with both AT-III and heparin cofactor II (HC-II) and it was more effective than unfractionated heparin of LMwt-heparin in enhancing the interaction of HC-II with thrombin.
Minix
R
R
Department of Chemistry, Prairie View A&M University TX 77446, USA.
Doctor
V M
VM
D000925:Anticoagulants / Q000378:metabolism*; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005342:Fibrinolysis / Q000187:drug effects*; D006487:Hemostasis; D006801:Humans; D007700:Kinetics; D010958:Plasminogen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000925:Anticoagulants; D017395:Plasminogen Activator Inhibitor 1; D011134:Polysaccharides; D000990:Antithrombin III; D010958:Plasminogen; C007789:fucoidan; D010450:Endopeptidases; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator