Enzyme urokinase-plasminogen activator system

Jl. Jensen, M. K., Riisbro, R., Holten-Andersen, M. N., et al.. Collagen metabolism and enzymes of the urokinase plasminogen activator system in chronic myeloproliferative disorders Correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism. Eur. J. Haematol. 71, 276-282 (2003). 

Tissue Plasminogen Aetivator (tPA). While streptokinase and urokinase can effectively induce clot dissolution in the majority of patients if given early, they lack clot specificity. Treatment with these enzymes results in a systemic lytic state attributable to their degradative action on circulating fibrinogen. Tissue plasminogen activator (tPA) was developed to achieve rapid and specific thrombolysis. 

The hypothesis that stress can modulate MMP expression is also supported by studies in mice. Using social isolation as a stressor, the mRNA levels of MMP-2, MMP-9, matrix-type matrix metalloproteinase-1 (MT1-MMP), and urokinase-type plasminogen activator were higher in the tumor and liver tissues of the isolated mice than in control mice.91 Furthermore, a recent study has shown that restraint stress causes an increase in expression of the plasminogen activator inhibitor-1, another key player in the plas-minogen/plasmin enzyme system in mice.92 As these enzymes have been described to have functions besides their role in ECM remodeling,93 studies on stress-related effects on MMP/TIMP balance have implications in the relationship between stress and cancer initiation and progression.. 

The role of the fibrinolytic system is to dissolve any clots that are formed within the intact vascular system and so restrict clot formation to the site of injury. The digestion of the fibrin and hence its lysis is catalysed by the proteolytic enzyme, plasmin, another serine proteinase. Plasmin is formed from the inactive precursor, plasminogen, by the activity of yet other proteolytic enzymes, urokinase, streptokinase and tissue plasminogen activator (tPA) which are also serine proteinases. These enzymes only hydrolyse plasminogen that is bound to the fibrin. Any plasmin that escapes into the general circulation is inactivated by binding to a serpin (Box 17.2). 

The normal tissue lysis activators are proteins. One such activator from the kidney is urokinase. This enzyme has not been found systemically, but only in the kidney and urine. It directly activates plasminogen to plasmin by hydrolysis of a small peptide from the plasminogen molecule. Other known enzymatic activators are streptokinase and brinase, which have been discussed elsewhere.82>83 Urokinase can be isolated from urine in small amounts. This has made it a very expensive material. Abbott Laboratories has developed a tissue culture technique in which kidney cells are grown under exacting conditions and urokinase is isolated.84 Recently Abbott Laboratories made a request to the FDA for a license to sell this form of urokinase called Abbokinase . This process should increase the availability of urokinase and decrease its cost. 

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