Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrin II monomer has a dramatic inhibitory effect on the rate of heparin-catalyzed inactivation of human alpha-thrombin by antithrombin III. At 6 microM fibrin II monomer, equivalent to the concentration of fibrinogen in plasma, the second-order rate constant was reduced by a factor of 308--from 2.05 x 10(8) M-1.s-1 to 6.65 x 10(5) M-1.s-1. Fibrin II monomer minimally affected the uncatalyzed rate of thrombin inactivation showing a reduction in the second-order rate constant by a factor of only 1.6. Fibrinogen and the product of plasmin degradation of fibrinogen, fragment E, at 6 microM concentrations also decreased the second-order rate constant for heparin-catalyzed thrombin inactivation, but by factors of only 2.7 and 1.9, respectively. On the basis of these observations it is proposed that protection of thrombin from inactivation by heparin-antithrombin III by fibrin II monomer can explain the limited efficacy of heparin in preventing coronary reocclusion in patients treated with tissue plasminogen activator and other fibrinolytic agents.
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PMID:Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. 272 39

Eicosapentaenoic acid (EPA), the precursor fatty acid of three series of prostaglandins, has been reported to have an antiatherothrombotic potential. We gave highly purified EPA in a soft capsule (90% ethylester form of EPA; EPA-E) to 6 healthy male volunteers for 4 weeks. After the administration of 900 mg/day of EPA-E for two weeks or longer, a significant reduction in plasma beta thromboglobulin level was observed, and after 4 weeks' administration, significantly blunted pressor responsiveness to infused angiotensin II was observed. These changes were not observed 4 weeks after EPA-E had been discontinued. After 4 weeks' ingestion of EPA-E, the platelet count, mean platelet volume, platelet aggregation with adenosine diphosphate or collagen, plasma recalcification time, prothrombin time, plasma antithrombin III, fibrinogen or plasmin concentrations, serum concentrations of total cholesterol, triglycerides, total phospholipid, nonesterified fatty acid or high-density lipoprotein cholesterol were unchanged. From the data presented it can be said that EPA-E causes a mild depression of vascular contractility and of platelet aggregability in vivo and exerts a beneficial influence on several cardiovascular factors.
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PMID:Effects of highly purified eicosapentaenoic acid on plasma beta thromboglobulin level and vascular reactivity to angiotensin II. 282 70

We have isolated three cDNA clones for human alpha 2-plasmin inhibitor (alpha 2-PI). Two clones are from human hepatoma cell line, Hep G2, and cover the entire protein coding region plus the 3'-flanking region up to the poly(A) sequence, and the other clone is from human liver and contains the carboxyl-terminal half. The total length of the cDNAs is 2.29 kb, corresponding to more than 95% of the full-length mRNA. alpha 2-PI seems to consist of 452 amino acid residues plus 39 amino acid residues for the signal peptide. The amino acid sequence shows 23 to 28% homology to those of five other protease inhibitors, plasminogen activator inhibitor (PAI), protein C inhibitor (PCI), alpha 1-antitrypsin (alpha 1-AT), antithrombin III (AT III), and alpha 1-antichymotrypsin (alpha 1-AC). alpha 2-PI seems to be the most distantly related among these inhibitors. Comparison of the phylogenetic trees of proteases and their inhibitors indicates that four proteases, namely elastase (or trypsin), chymotrypsin, plasminogen activator, and thrombin, may have evolved concurrently with the corresponding inhibitors. However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates. The data suggest that alpha 2-PI may originally have inhibited some protease other than plasmin, and protein C may have had an inhibitor different from the present one early in its evolutionary history.
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PMID:Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence. 283 Feb 48

Hedgehog plasma was separated by gel filtration on Sephacryl S-200, the fractions resolved by electrophoresis and the electrophoretograms characterized for collagenase, papain and plasmin inhibiting activities with the high mol. wt substrate casein. The three inhibitors previously identified as alpha 2-, alpha 2-beta- and beta-macroglobulins were found to inhibit all three proteases. These were the only collagenase inhibitors found in plasma. Hedgehog alpha 2-chymotrypsin inhibitor and beta-protease inhibitor were both found to also inhibit papain. Three new inhibitors specific for papain (gamma-, alpha 2- and alpha 1-cysteine protease inhibitors) and one for plasmin (alpha 2-antiplasmin) were also found, bringing the number of protease inhibitors in hedgehog plasma to 14. Immunological cross-reactivity as studied by immunoelectrophoresis showed homology between hedgehog alpha 2-macroglobulin and rat murinoglobulin I and between hedgehog alpha 2-antithrombin and rat antithrombin III.
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PMID:Further studies of plasma protease inhibitors in the hedgehog, Erinaceus europaeus; collagenase, papain and plasmin inhibitors. 288 40

In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis. The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation. In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase. The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically. The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease. The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins. The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g. concentrates of AT III, PPSB, or fresh frozen plasma. The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome".
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PMID:The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia. 293 57

A proteinase inhibitor has been isolated from human colorectal adenocarcinomas by extraction with a low-ionic-strength buffer and a combination of Con A-Sepharose, Sephadex G-200, DEAE-cellulose and chromatofocusing steps. The preparation appeared to be homogeneous upon gel exclusion chromatography and SDS-polyacrylamide gel electrophoresis and had an estimated molecular weight of 66,000. The inhibitor was able to bind and inhibit urokinase, plasmin, trypsin, tissue plasminogen activator and thrombin. The binding appeared to be stoichiometric and relatively fast. The isoelectric point of the protein was 4.6-4.7. The inhibitor did not crossreact with antisera elicited against alpha 2-macroglobulin, alpha 2-antiplasmin, antithrombin III or C1-inhibitor, but it did crossreact with an antiserum against alpha 1-antitrypsin in double immunodiffusion. The antiserum only partially attenuated the activity of the inhibitor. Whereas alpha 1-antitrypsin completely inhibited the amidolytic activity of elastase, the tumor inhibitor had no effect on elastase under the same conditions.
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PMID:Isolation and partial characterization of a proteinase inhibitor from human colorectal adenocarcinoma. 293 82

The amidolytic plasmin activity of a mixture of tissue plasminogen activator (tPA) and plasminogen is enhanced by heparin at therapeutic concentrations. Heparin also increases the activity in mixtures of urokinase-type plasminogen activator (uPA) and plasminogen but has no effect on streptokinase or plasmin. Direct analyses of plasminogen activation by polyacrylamide gel electrophoresis demonstrate that heparin increases the activation of plasminogen by both tPA and uPA. Binding studies show that heparin binds to various components of the fibrinolytic system, with tight binding demonstrable with tPA, uPA, and Lys-plasminogen. The stimulation of tPA activity by fibrin, however, is diminished by heparin. The ability of heparin to promote plasmin generation is destroyed by incubation of the heparin with heparinase, whereas incubation with chondroitinase ABC or AC has no effect. Also, stimulation of plasmin formation is not observed with dextran sulfate or chondroitin sulfate A, B, or C. Analyses of heparin fractions after separation on columns of antithrombin III-Sepharose suggest that both the high-affinity and the low-affinity fractions, which have dramatically different anticoagulant activity, have similar activity toward the fibrinolytic components.
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PMID:Interaction of heparin with plasminogen activators and plasminogen: effects on the activation of plasminogen. 294 15

Thrombin and plasmin are inactivated by antithrombin III at different rates. Heparin, at a catalytic amount, increases primarily the inactivation rate of thrombin. The two proteinases compete for heparin, i.e. heparin is preferably attached by thrombin. Furthermore, fibrinogen as well as fibrin protect plasmin against inactivation by antithrombin III. However, at high concentration of heparin, plasmin inactivation by antithrombin III is accelerated even in the presence of fibrinogen or fibrin.
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PMID:Sensitivity of thrombin and plasmin to heparin and antithrombin III. 294 48

Indices of fibrinogen cleavage by thrombin (fibrinopeptide A, FPA); by plasmin (BB1-42 and serum FDP); of the platelet release reaction (beta thromboglobulin and platelet factor 4); and antithrombin III (AT III) levels were measured serially in 46 patients with pulmonary emboli in whom either substantial (SR) or impaired (IR) resolution was documented. The mean FPA level in the 25 patients with IR was significantly higher than the level in the 21 patients with SR (p less than 0.01). The increased thrombin activity in the IR group was not due to AT III deficiency or increased platelet reactivity but the elevated FPA levels in the presence of therapeutic levels of anticoagulation indicated that the dose of heparin was inadequate. The higher BB1-42 and FDP levels in this group reflected the increased plasmin activity that follows increased thrombin activity. In a multivariate discriminant analysis, only the FPA data could be used to predict the degree of resolution. Increased thrombin action impairs resolution presumably by producing greater amounts of accreted fibrin on the impacted embolus.
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PMID:Indices of fibrinogen proteolysis and platelet activation during the resolution of pulmonary embolism. 295 58

The inhibiting action in vitro of urinastatin on blood coagulation was studied for the purpose of therapeutic application against thrombotic disorders, and the following results were obtained: 1) Partial thromboplastin time of normal human plasma was prolonged dose-dependently by the addition of urinastatin to the reaction mixture, but prothrombin time was little inhibited by the addition of urinastatin. Thrombin time was also prolonged with urinastatin dose-dependently. 2) Using chromogenic synthetic peptide substrates, the amydolytic activities of XIIa, plasma kallikrein and Xa activated with RVV were inhibited by the addition of urinastatin to the reaction mixtures. 3) Activated partial thromboplastin time of normal plasma was prolonged by the addition of urinastatin or heparin, and simultaneous application of both urinastatin and heparin to the reaction mixture resulted in an additional inhibitory effect on APTT. Therefore, it was assumed that the different molecular structures of the clotting factors were concerned with the inhibitory actions of urinastatin and antithrombin III. Furthermore, urinastatin was indicated to have an important role in antithrombotic remedy, since it has no inhibitory action against protein C. 4) In the comparison with purified human plasmin and plasma plasmin activated with streptokinase, the strong inhibitory action of urinastatin on purified plasmin was demonstrated, but the inhibitory action of urinastatin was decreased markedly in plasma. Therefore, it is suggested that plasma may contain an inhibitory factor against the action of urinastatin.
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PMID:[In vitro observations on antithrombotic action of urinastatin]. 296 16


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