Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four protease inhibitors have been identified in human serum and methods for their isolation are described. After removal of the euglobulin fraction, serum was submitted to ion exchange chromatography and gel filtration, and fractions were tested for inhibition of the lysis of plasminogen-deficient fibrin clots by plasmin, trypsin and elastase. In addition inhibitors of plasminogen activation were sought by studying the effects of separated fractions on the lysis of plasminogen-rich fibrin clots by urokinase. Examination by immunophoresis showed that three of the separated inhibitors were alpha2-macroglobulin, alpha1-antitrypsin and inter-alpha-trypsin inhibitor. The fourth antiprotease was a powerful inhibitor of both urokinase-induced and plasmin-induced clot lysis, and was identified as an inter-alpha-globulin from its electrophoretic mobility in agarose gels.
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PMID:Serum inhibitors in fibrinolysis. 5 65

1. Human plasma contains a variety of proteins that are capable of inhibiting plasmin activity. Whole plasma possesses 'rapid' and 'progressive' plasmin-neutralizing activity: this study assesses the contribution of individual protease inhibitors to this plasmin-neutralizing property of plasma. 2. Rapid and progressive antiplasmin activities of human plasma correlate with alpha2-macroglobulin and alpha1-antitrypsin concentrations respectively. 3. Fluctuations in the amounts of the other measured inhibitors (antithrombin III, Cl in activator and inter-alpha-tryspin inhibitor) did not influence the measured antiplasmin activity.
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PMID:The contribution of plasma protease inhibitors to antiplasmin activity in man. 6 Jan 90

Pig plasmin (Lysofibrin) was given to 11 patients with phlebographically verified venous thrombosis, 2 of whom were treated two and three times, respectively. The effect on coagulation and fibrinolytic parameters was studied. The platelet count, Owren's P&P (prothrombin plus factors VII and X), plasminogen, factor XIII, and antithrombin III did not change during the treatment. All patients developed a proteolytic activity demonstrable on both unheated and heated fibrin plates. The fibrinogen decreased successively to very low levels, and parallel to this an increase in fibrin/fibrinogen degradation products was found. The factor VIII and factor V activities decreased immediately after each Lysofibrin infusion but normalized rapidly again. The factor VIII molecule, however, retained its reactivity to rabbit antiserum against factor VIII. Immediately after the plasmin infusion a decrease of both alpha2-macroglobulin (alpha2-M) and the rapidly reacting alpha2-antiplasmin was observed. alpha2-M decreased successively and in several of the patients values were unmeasurable for a period of some days. A complex formation between pig plasmin and the alpha2-antiplasmin was demonstrated in crossed immunoelectrophoresis. The complexes were rapidly cleared from the circulation. No interaction between the pig plasmin and the inhibitor of the plasminogen activation, alpha1-antitrypsin or inter-alpha-inhibitor, was found.
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PMID:Effects of porcine plasmin on the coagulation and fibrinolytic systems in humans. 7 91

Simultaneous to the liberation of the acid stable trypsin-plasmin-inhibitor from the inter-alpha-trypsininhibitor in vivo, acid labile degradation products are set free. The main product can be estimated by immunological methods. This product is not excreted by the kidney in contrast to the acid stable inhibitor. The product accumulates in serum in different diseases. An increased concentration of this product indicates also an increased turn-over of the inter-alpha-trypsin inhibitor in the case when the concentraton of the intact inter-alpha-trypsin inhibitor or of the filtrable derivative are within normal range.
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PMID:[About degradation products of the inter-alpha-trypsin inhibitor in serum. II. Acid label derivatives of the inter-alpha-trypsin inhibitor (author's transl)]. 85 85

In our previous research, we found that the level of the plasminogen activity in the plasma from Duchenne-type patients with progressive muscular dystrophy was higher than of the normal boys, though the level of the plasmin inhibitors was lower. Therefore, in the present study, we investigated the differences in the fractions of plasmin inhibitors. The subjects were nine patients (the average age being 17.1 years) who had been diagnosed, by clinical and biochemical tests, as having PMD; serving as controls were normal boys (the average age being 15 years), the patients' mothers, and the mothers of the normal boys. The plasmin inhibitors were separated from plasma using lysine-Sepharose columns according to the method of Urita et al. The determination was performed based on the method of Aoyagi et al. and an immunoreactive assay. The results were as follows: (1) No significant differences were seen between patients with PMD and control subjects with respect to either alpha 1-antichymotrypsin, antithrombin III, and alpha 1-antitrypsin or alpha 2-macroglobulin and inter-alpha-trypsin inhibitors. These results suggested that the low level of plasmin inhibitors in patients was due to the low activity of the C1 inactivator. (2) The patients with PMD showed lower values than the normal boys in the levels of C1 inactivator in plasma; similarly, the mothers of these patients showed lower values than the normal mothers.
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PMID:Plasma plasmin inhibitors in Duchenne-type progressive muscular dystrophy. 316 Mar 43

Urokinase-activated human plasma was studied by gel electrophoresis, gel filtration, crossed immunoelectrophoresis and electroimmunoassay with specific antibodies and by assay of esterase and protease activity of isolated fractions. Urokinase induced the formation of different components with plasminogen+plasmin antigenicity. At low concentrations of urokinase, a component with a K(D) value of 0.18 by gel filtration and post beta(1) mobility by gel electrophoresis was detected. The isolated component had no enzyme or plasminogen activity. In this plasma sample fibrinogen was not degraded for 10h, but when fibrin was formed, by addition of thrombin, fibrin was quickly lysed, and simultaneously a component with a K(D) value of 0 and alpha(2) mobility appeared, which was probably plasmin in a complex with alpha(2) macroglobulin. This complex showed both esterase and protease activity. After gel filtration with lysine buffer of the clotted and lysed plasma another two components were observed with about the same K(D) value by gel filtration as plasminogen (0.35), but beta(1) and gamma mobilities by gel electrophoresis. They appeared to be modified plasminogen molecules, and possibly plasmin with gamma mobility. Similar processes occurred without fibrin at higher urokinase concentrations. Here a relatively slow degradation of fibrinogen was correlated to the appearance of the plasmin-alpha(2) macroglobulin complex. The fibrin surface appeared to catalyse the ultimate production of active plasmin with a subsequent preferential degradation of fibrin and the formation of a plasmin-alpha(2) macroglobulin complex. The gel filtration and electrophoresis of the plasma protease inhibitors, alpha(1) antitrypsin, inter-alpha-inhibitor, antithrombin III, and C(1)-esterase inhibitor indicated that any complex between plasmin and these inhibitors was completely dissociated. The beta(1) and post beta(1) components appear to lack correlates among components occurring in purified preparations of plasminogen and plasmin.
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PMID:Different molecular forms of plasminogen and plasmin produced by urokinase in human plasma and their relation to protease inhibitors and lysis of fibrinogen and fibrin. 428 70

TNF-stimulated gene 6 (tsg6), encoding a 35-kDa secretory glycoprotein (TSG-6), is induced in fibroblasts, chondrocytes, synovial cells, and mononuclear cells by the proinflammatory cytokines TNF-alpha and IL-1, or by LPS. Large amounts of TSG-6 protein were found in synovial fluids of patients with rheumatoid arthritis. TSG-6 protein forms a stable complex with components of the serine protease inhibitor, inter-alpha-inhibitor (I alpha I). In this work, we show that TSG-6 potentiates the inhibitory effect of l alpha l on the protease activity of plasmin. The plasmin/plasminogen activator system is important in the protease network associated with inflammation. To test the hypothesis that through their cooperative inhibitory effect on plasmin TSG-6 and l alpha l can modulate the protease network and thus inhibit inflammation, we examined the effect of TSG-6 on experimentally induced inflammation. Human recombinant TSG-6 protein showed a potent anti-inflammatory activity in the murine air pouch model of carrageenan- or IL-1-induced acute inflammation. The inhibitory effect of locally administered TSG-6 on the IL-1-induced cellular infiltration was comparable with that of systemic dexamethasone treatment. Two mutant TSG-6 proteins with single amino acid substitutions close to the N terminus showed a complete or partial loss of anti-inflammatory activity. The anti-inflammatory effect of the TNF/IL-1-inducible TSG-6 protein, along with its ability to inhibit protease action through interaction with l alpha l, suggests that TSG-6 production during inflammation is part of a negative feedback loop operating through the protease network.
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PMID:TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo. 856 67

The pro-inflammatory cytokines IL-1 and TNF-alpha are primary mediators of the acute phase response, the complex reaction of the mammalian organism to infection and injury. Among the genes activated by TNF-alpha and IL-1 in a variety of cells is TNF-stimulated gene 6 (TSG-6). The TSG-6 cDNA encodes a secreted 35 kDa glycoprotein which is abundant in synovial fluids of patients with various forms of arthritis and detectable in serum of patients with different inflammatory or autoimmune disorders. TSG-6 protein consists of two structural domains: a hyaluronan-binding link module, the characteristic domain of the hyaladherin family of proteins, and a C-terminal CUB domain, present in a variety of diverse proteins. TSG-6 forms a stable complex with components of the plasma protein inter-alpha-inhibitor (I[alpha]I), a Kunitz-type serine protease inhibitor. TSG-6 and I(alpha)I synergize to inhibit plasmin, a serine protease involved in the activation of matrix metalloproteinases which are part of the proteolytic cascade associated with inflammation. Recombinant human TSG-6 protein exerts a potent anti-inflammatory effect in a murine model of acute inflammation. Modulation of the proteolytic network associated with inflammatory processes may be a mechanism whereby TSG-6, in cooperation with I(alpha)I, inhibits inflammation. Activation of the TSG-6 gene by pro-inflammatory cytokines, presence of TSG-6 protein in inflammatory lesions and its anti-inflammatory effect suggest a role for TSG-6 in a negative feed-back control of the inflammatory response.
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PMID:TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity. 924 9

Bikunin is a plasma proteinase inhibitor that has received little attention in the past, probably because its activity towards various proteinases was found to be relatively weak in early work. It was recently discovered, however, that bikunin effectively inhibits a proteinase that seems to be involved in the metastasis of tumour cells--cell surface plasmin--and that a fragment of bikunin inhibits two proteinases of the coagulation pathway--factor Xa and kallikrein. Furthermore, it has been found that bikunin has other properties, such as the ability to modulate cell growth and to block cellular calcium uptake. Most of the bikunin in the blood occurs as a covalently linked subunit of the proteins pre- and inter-alpha-inhibitor. In this form bikunin lacks some of its known activities, and there is evidence that its release by partial proteolytic degradation may function as a regulatory mechanism. Although the physiological function of bikunin still remains to be established, current data suggest that this protein plays a role in inflammation. Further studies could therefore lead to results of therapeutical value.
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PMID:Bikunin--not just a plasma proteinase inhibitor. 1068 49

A glycoprotein with a high inhibitory activity against trypsin was isolated in 1961 from human plasma and named inter-alpha trypsin inhibitor (ITI). Since then, several other proteins that share antigenic and structural similarities with ITI have been identified and classified as members of the ITI protein family. These glycoproteins built up from different combinations of four polypeptides HC1, HC2, HC3 and bikunin are encoded by four genes H1, H2, H3, L on three chromosomes. Bikunin has two proteinase inhibitor domains and belongs to the Kunitz-type protease inhibitor family; it displays an inhibitory activity against trypsin, leukocyte elastase and plasmin. The heavy chains do not have any protease inhibitory properties but have the capacity to interact in vitro and in vivo with hyaluronic acid. This binding promotes the stability of the extra-cellular matrix. Consequently, the ITI protein family is suspected of playing a key role in the extra-cellular matrix biology. Isolation of free heavy chains in bronchial secretions and the recent emphasis about the bikunin role in tumoral invasion should enhance the interest about ITI protein family in the pathophysiology of chronic bronchopulmonary diseases or lung cancer progression.
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PMID:[Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix]. 1085 62


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