The activation of Glu- and Lys-plasminogens by streptokinase: effects of fibrin, fibrinogen and their degradation products.
Studies were performed on the activation of a native form of human plasminogen (Glu-plg) or its degraded form (Lys-plg) by streptokinase (SK) in the presence of fibrin, fibrinogen, SK-potentiator, fragment D or E. When Glu-plg (0.1 microM) was activated by 0.5 u/ml of SK in the presence of 100 micrograms of S-2251 and 0.1 microM of fibrin, fibrinogen or their degradation products (potentiating agents), fibrin enhanced the rate of the hydrolysis of S-2251 to the largest extent. Fragments D and E only slightly enhanced it. The order of effectiveness of enhancement was fibrin greater than SK-potentiator greater than fibrinogen greater than D greater than E. When Lys-plg (0.1 microM) was activated by 0.5 u/ml of SK in the presence of potentiating agents, SK-potentiator enhanced the hydrolysis of S-2251 to the largest extent. The enhancement was far less in comparison to the enhancement of the hydrolysis by Glu-plg and SK. The measurement of delta OD405/min at the time of 50% hydrolysis of the substrate was performed in order to compare the effects of concentrations of potentiating agents. The maximum enhancement was obtained at almost an equimolar ratio of plasminogen and fibrin. Fifty percent enhancement was obtained at 0.05 microM for SK-potentiator, 0.072 microM for fibrinogen, 0.21 microM for D and 0.35 microM for E. Fibrin caused the largest extent of enhancement among other potentiating agents. These results may indicate that a trimolecular complex between SK, plasminogen and potentiating agents hydrolyzes S-2251 more effectively than SK-plasminogen complex, thus a trimolecular complex being a better activator than SK-plasminogen complex. Although D and E enhanced only slightly the rate of hydrolysis of S-2251 at equimolar ratio to plasminogen, increase in their concentration resulted in the same extent of enhancement as shown in the presence of fibrinogen or SK-potentiator.
D005337:Fibrin / Q000494:pharmacology*; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D013053:Spectrophotometry; D013300:Streptokinase / Q000494:pharmacology*
D005338:Fibrin Fibrinogen Degradation Products; D009842:Oligopeptides; D010446:Peptide Fragments; C018998:lysyl-plasminogen; C018788:valyl-leucyl-lysine 4-nitroanilide; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D013300:Streptokinase