Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the interaction of alpha 2-macroglobulin (alpha 2M) with the serine proteinase urokinase, an activator of plasminogen. Urokinase formed sodium dodecyl sulfate stable complexes with purified alpha 2M and with alpha 2M in plasma. These complexes could be visualized after polyacrylamide gel electrophoresis by protein blots using 125I-labeled anti-urokinase antibody or by fibrin autography, a measure of fibrinolytic activity. According to gel electrophoretic analyses under reducing conditions, urokinase cleaved alpha 2M subunits and formed apparently covalent complexes with alpha 2M. Urokinase cleaved only about 60% of the alpha 2M subunits maximally at a mole ratio of 2:1 (urokinase: alpha 2M). Binding of urokinase to alpha 2M protected the urokinase active site from inhibition by antithrombin III-heparin and inhibited, to a significant extent, plasminogen activation by urokinase. Reaction of urokinase with alpha 2M caused an increase in intrinsic protein fluorescence and, thus, induced the conformational change in alpha 2M that is characteristic of its interactions with active proteinases. Our results indicate that both in plasma and in a purified system the alpha 2M-urokinase reaction is functionally significant.
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PMID:Structural and functional characterization of the inhibition of urokinase by alpha 2-macroglobulin. 241 80

The lytic therapy using Urokinase (UK) as well as Streptokinase (SK) has a significant risk of complications such as systemic bleeding. We aimed to develop the autologous plasmin (AP) solution as a potential lytic agent and to evaluate its lytic efficacy. Method; The AP solution was aseptically prepared by adding UK to autologous plasma separated by centrifugation (at 4 degrees C, 3,000 rpm, 10 min). The induced plasmin activity of the AP solution was measured by plasminogen-free fibrin plate method and spectrophotometric method with substrate S-2251. In vitro study, we made a fibrin clot by adding CaCl2 (1/40 mole, 0.2 ml) to autologous plasma (0.2 ml). The clot weight was measured before and after incubation for 60 min at 37 degrees C to estimate the lytic effects of the AP solution and the UK solution. In animal study, femoral artery of anesthetized mongrel dogs (n = 20) was narrowed by ligation (1 mm in diameter) and the fibrin clot was embolized into this portion. AP (n = 8), UK (n = 6) or saline (n = 6) was selectively injected for 3 min into the arterial lumen, after the temporary flow obstruction was completed by inflation of balloon tip catheter located proximal to the embolized site of the artery. Lytic effects on the embolized fibrin clot were sequentially observed by the extra-vascular ultrasound flow meter (equipped with pencil probe) for 60 min. For this study, the AP solution was prepared by adding dose of 12,000 IU/ml of UK. The same dose of the UK solution was also used as a control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The potential thrombolysis under selective infusion of the autologous plasmin (AP) solution]. 296 1

The effect of tissue plasminogen activator (TPA) or urokinase on the specific binding of human Glu-plasminogen to fibrin I formed in plasma by clotting with Reptilase was studied using 125I-plasminogen and 131I-fibrinogen. In the absence of TPA, small amounts of plasminogen were bound to fibrin I. TPA induced binding of plasminogen to plasma fibrin I that was dependent upon the concentrations of TPA and plasminogen as well as upon the time of incubation. Plasminogen binding occurred in association with fibrin clot lysis and the formation in the clot supernatant of alpha 2-plasmin inhibitor-plasmin complexes. Urokinase also induced binding of plasminogen to plasma fibrin I that was concentration- and time-dependent. The molecular form of plasminogen bound to the fibrin I plasma clot was identified as Glu-plasminogen by dodecyl sulfate-polyacrylamide gel electrophoresis and by fast performance liquid chromatography. Further studies demonstrated that fibrin I formed from fibrinogen that had been progressively degraded by plasmin-bound Glu-plasminogen. The mole ratio of plasminogen bound increased with the time of plasmin digestion. Glu-plasminogen did not bind to fibrin I formed from fibrinogen progressively digested by human leukocyte elastase, thereby demonstrating the specificity of plasmin. These studies demonstrate that plasminogen activators regulate the binding of Glu-plasminogen to fibrin I by catalyzing plasmin-mediated modifications in the fibrin substrate.
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PMID:Tissue plasminogen activator and urokinase mediate the binding of Glu-plasminogen to plasma fibrin I. Evidence for new binding sites in plasmin-degraded fibrin I. 315 57