Streptokinase-dependent delayed activation of horse plasminogen.

This research study has conducted an investigation into the differential activation rates of horse plasminogen (a precursor of the enzyme plasmin) by streptokinase depending on their molar ratios. The study further explores whether horse plasminogen activation could be used as a model representation for the activation of certain unusual types of human plasminogens.

Study Methodology and Findings

• The research involved observing the activation of purified horse plasminogen to plasmin using varying ratios of streptokinase. The pertinent finding was that as the ratio of streptokinase to plasminogen decreases, complete activation occurs faster. At the highest ratio of 1:10, it took only five minutes, but it took 15-30 minutes at a 1:1 ratio, and a 6:1 ratio required 120 – 180 minutes.
• This delay in the activation of plasmin is theorized to be due to challenges in the formation of the streptokinase-plasminogen complex, as suggested by gel filtration studies involving isotopically labeled streptokinase and horse plasminogen.
• The study also found that the majority streptokinase unit within the streptokinase-plasmin complex (which emerges from the streptokinase-plasminogen complex) had a molecular weight of approximately 25,000 daltons.
• The streptokinase-horse plasmin complex could activate bovine plasminogen, exhibiting relative stability. The native streptokinase experienced rapid modification by horse plasmin, mostly generating a fragment with a molecular weight much like that of the streptokinase constituent within the horse streptokinase-plasmin complex.

Comparison of Horse and Human Plasminogen

• The researchers partially characterized horse plasminogen and found it to be similar to human plasminogen in terms of molecular weight, N-terminal analysis, and amino acid composition, with a few specific differences.
• One difference noted was horse plasminogen’s lack of reaction with antibodies to human plasminogen, and its isoenzymes were determined to be more acidic than those found in humans.
• Based on these findings, the researchers argue that further characterization of horse plasminogen is needed to ascertain whether the activation mechanism by streptokinase can serve as a model for the altered activation kinetics of certain unusual types of human plasminogen.