Effect of fucoidan during activation of human plasminogen

• Published in: Thrombosis research Vol. 79; no. 3; pp. 237 - 247
• Main Authors: Doctor, V.M., Hill, C., Jackson, G.J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 01.08.1995; Elsevier Science
• Subjects: Amino Acid Sequence; Aminocaproic Acid - pharmacology; Anticoagulants - pharmacology; Antifibrinolytic Agents - pharmacology; Biological and medical sciences; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Fibrinogen - pharmacology; fibrinolysis; Fibrinolytic Agents - metabolism; fucoidan; General pharmacology; Humans; Medical sciences; Molecular Sequence Data; Oligopeptides - metabolism; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plasminogen - metabolism; Plasminogen Activators - pharmacology; Polysaccharides - pharmacology; streptokinase; Streptokinase - metabolism; t-PA; urokinase; streptokinase; fibrinolysis; fucoidan; urokinase; t-PA; Human; Blood coagulation; u-Plasminogen activator; Serine endopeptidases; Enzyme; Algae; Activation; Anticoagulant; Fibrinolysis; In vitro; Biological activity; t-Plasminogen activator; Phaeophycophyta; Fucus vesiculosus; Plant origin; Hydrolases; Proteinases; Thallophyta
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(95)00111-4

Fucoidan [sulfated poly (L-fucopyranose)] was compared with 6-aminohexanoic acid (6-AH) or CNBr-cleaved fibrinogen (CNBr-Fbg) alone or in combination in enhancing the activation of glutamic plasminogen (Glu-Plg) or lysine plasminogen (Lys-Plg) by two-chain tissue plasminogen activator (t-PA) or LMwt-urokinase or by streptokinase. Fucoidan enhanced the t-PA activation of Glu-Plg or Lys-Plg at Plg concentrations greater than 75nM, while stimulation by CNBr-Fbg of t-PA activation followed saturation kinetics of Michaelis-Menton. During t-PA activation of Glu-Plg, a high degree of synergism was observed between 6-AH and fucoidan while the enhancement by CNBr-Fbg was not influenced by fucoidan and was reversed by 6-AH. Fucoidan alone at higher concentrations was effective in enhancing the activation of Glu-Plg by urokinase while the combination of fucoidan and 6-AH showed additive effect in enhancing the activation of Lys-Plg. The activation of Glu-Plg by streptokinase was reversed by fucoidan in a manner similar to that reported for 6-AH. The results are interpreted to suggest that CNBr-Fbg and 6-AH compete with each other for the same lysine binding sites (LBS) on the Plg molecule while fucoidan acted synergistically with 6-AH in enhancing the t-PA activation of Glu-Plg by a different mechanism. The double reciprocal plot for the interaction of Glu-Plg and urokinase also showed a significantly higher affinity between the two in presence of fucoidan.