Effect of fucoidan during activation of human plasminogen.
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.
Chemistry Department, Prairie View A&M University, Tx 77446, USA.
V M
VM
Doctor
C
C
Hill
G J
GJ
Jackson
D000595:Amino Acid Sequence; D015119:Aminocaproic Acid / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005340:Fibrinogen / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D013300:Streptokinase / Q000378:metabolism
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D005343:Fibrinolytic Agents; D009842:Oligopeptides; D011134:Polysaccharides; C018788:valyl-leucyl-lysine 4-nitroanilide; D005340:Fibrinogen; D010958:Plasminogen; C007789:fucoidan; D013300:Streptokinase; D010960:Plasminogen Activators; D015119:Aminocaproic Acid