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)

It has been established that a bromelain plasminogen activator will produce plasmin in rat experiments. In addition the plasmin cleaves Hageman factor in a way that leads to a strong release of kallikrein but a weak release of thrombin. A possible mechanism is suggested to explain how the body can maintain thrombin at a level too low to cause platelet aggregation but adequate to stimulate release of prostaglandins and enzymes for more than 24 hours from a single dose of the pineapple enzymes. Since bromelain therapy leads to formation of platelets with increased resistance to aggregation, it is obvious that the dominant endogenous prostaglandins being produced must be from the group that increases platelet cyclicAMP levels (prostacyclin, PGE1, etc.). The combination of fibrinolytic and antithrombic properties appear to be effective and two large scale tests on heart patients have shown a practically complete elimination of thrombosis.
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PMID:Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients. 625 12

Various flower bulbs and vegetable and legume seeds were tested for inhibitors of polymorphonuclear leukocyte elastase, pancreatic elastase, cathepsin G, cathepsin B, trypsin, alpha-chymotrypsin, Hageman factor fragments, plasma kallikrein, and plasmin. Calla bulbs contained a 33,000 dalton polymorphonuclear leukocyte elastase inhibitor and a 4,000 dalton cathepsin G inhibitor. Seeds of some members in the Cruciferae family, such as radish and broccoli, were found to contain one or more 2,500-4,000 dalton inhibitors which inhibited cathepsin G, trypsin, Hageman factor fragments, and plasmin, but not plasma kallikrein. These seeds also contained a 1,000 dalton cathepsin B inhibitor. The above inhibitors were probably polypeptides which inhibited proteinases by making an enzyme-inhibitor complex, with the exception of the cathepsin B inhibitor. These newly found inhibitors with their characteristic profiles of inhibition should be useful in biochemical and pathophysiological studies on granulocyte proteinases and enzymes of the coagulation and fibrinolytic pathways.
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PMID:Survey of plant inhibitors of polymorphonuclear leukocyte elastase, pancreatic elastase, cathepsin G, cathepsin B, Hageman factor fragments, and other serine proteinases. 634 Jun 94

A 42-yr-old woman with systemic lupus erythematosus without bleeding diathesis developed a prolonged activated partial thromboplastin time that was not corrected by normal plasma. An inhibitor that acted rapidly and inactivated 0.5 U/ml plasma thromboplastin antecedent (PTA, factor XI) at a 1:200 plasma dilution was demonstrated. In addition to a low titer of PTA (less than 0.01 U/ml), plasma assayed at 20-fold dilution also showed low titers of Hageman (factor XII, 0.02 U/ml), Fletcher (plasma prekallikrein, 0.02 U/ml), and Fitzgerald (high molecular weight kininogen, less than 0.01 U/ml) factors. The titer of these factors, except PTA, returned to normal upon further plasma dilution or upon removal of the inhibitor by protein A adsorption. Thus, the inhibitor appeared to interfere with these clotting factor assays, possibly by inactivating PTA in the substrate plasmas in the test system. Its specificity was further confirmed. The inhibitor did not interfere with surface-induced proteolytic cleavage of Hageman factor. Surface-induced generation of plasma kallikrein activity (amidolysis of H-D-pro-phe-arg-pNa and cold-promoted factor VII activity enhancement) requires only Hageman, Fletcher, and Fitzgerald factors and was normal. Reactions requiring all 4 contact phase factors, including PTA, such as surface-induced generation of plasmin activity (amidolysis of H-D-val-leu-lys-pNa) and activated Christmas factor (factor IXa) activity, were defective. Furthermore, the inhibitor bound to agarose-protein A inactivated and removed PTA selectively from normal plasma. The inhibitor was an IgG-lambda autoantibody that precipitated PTA. The inactivated activated PTA (factor XIa) without the requirement for an additional cofactor. Furthermore, it inhibited surface-induced activation of PTA by interfering with its proteolytic cleavage upon glass surface exposure and with its binding onto the reactive surfaces.
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PMID:A unique precipitating autoantibody against plasma thromboplastin antecedent associated with multiple apparent plasma clotting factor deficiencies in a patient with systemic lupus erythematosus. 642 50

Activation of bovine plasma prekallikrein was investigated with several proteinases. Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC 3.4.21.8] by bovine activated Hageman factor, trypsin [EC 3.4.21.4] and Pronase P (proteinases from Streptomyces griseus) and more gradually by papain [EC 3.4.22.2] and ficin [EC 3.4.22.3]. Activation of prekallikrein was also observed with bovine plasmin [EC 3.4.21.7], but not with bovine clotting factors Xa (Stuart factor) [EC 3.4.21.6] and IXa (Christmas factor) or thrombin [EC 3.4.21.5]. Urokinase [EC 3.4.99.26], Reptilase, collagenase [EC 3.4.24.3], elastase [EC 3.4.21.11], alpha-chymotrypsin [EC 3.4.21.1], Nagarse [EC 3.4.21.14], and stem bromelain [EC 3.4.22 4] did not convert prekallikrein to kallikrein. Plasma kallikrein activated to Hageman factor released kinin rapidly from bovine high molecular weight (HMW) kininogen. However, from bovine low molecular weight (LMW) kininogen, liberation of kinin was extremely slow. The kallikrein activity was inhibited by soybean trypsin inhibitor (SBTI), Trasylol, diisopropylfluorophosphate (DFP), and N-alpha-tosyl-L-lysine chloromethylketone (TLCK), but not by egg-white trypsin inhibitor (EWTI), lima bean trypsin inhibitor (LBTI), heparin or hexadimethrine bromide (Polybrene). The kallikrein formed an enzyme-inhibitor complex with SBTI and Trasylol, but not with LBTI. Prekallikrein did not react with SBTI. Prekallikrein consists of a single polypeptide chain of molecular weight about 90,000, as estimated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Activation of prekallikrein by Hageman factor was found to involve cleavage of the single peptide bond on the disulfide-bridged polypeptide chain, and no change of molecular weight was observed during the activation. The peptide bond cleaved in prekallikrein by the activation was an Arg-X peptide bond on a disulfide-bridged polypeptide chain.
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PMID:Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor. 676 24

Using a rabbit anti-human prekallikrein antibody crossed immunoelectrophoresis (CIE) and Laurell rocket antigen determinations were done in plasma of subjects with Fletcher (prekallikrein, PKA), Fitzgerald (high molecular weight kininogen), Hageman (XII), and PTA (XI) deficiencies as well as in patients with activation of coagulation (intravascular coagulation syndromes). Abnormal CIE patterns were seen in the Fletcher and Fitzgerald deficient plasmas and also in some of the patients with intravascular coagulation. In vitro studies of plasma treated with thrombin, plasmin, and contact activating agents indicated that abnormal CIE patterns and increased PKA antigen levels were indicative of activation of the Hageman factor dependent pathway and not the result of plasma clotting by thrombin. In vivo activation of the Hageman factor dependent pathway frequently results in an abnormal CIE and a low PKA antigen level.
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PMID:Immunoelectrophoretic studies of prekallikrein in human plasma. 691 63

Activation of the classical complement pathway is initiated by immune complexes consisting of IgM antibody or IgG subclasses 1, 2, and 3. Binding to Clq leads to activation of C1s and digestion of C4 and C2 to yield a C3 convertase. The alternative complement pathway is initiated by complex polysaccharides as well as immune complexes of the IgA class which interact with Factors B, D, C3, and properdin to yield a stabilized C3 convertase consisting of PC3Bb. Cleavage of C3 and C5 by either pathway yields the C3a and C5a anaphylatoxins which cause histamine release from mast cells and formation of the C5b6789 attack complex causes cell lysis. Both immunologic and nonimmunologic tissue damage can initiate the surface dependent pathways of coagulation, fibrinolysis, and kinin formation. Surface bound Hageman Factor interacts with complexes of prekallikrein and HMW-kininogen as well as Factor XI and HMW-kininogen to form activated Hageman factor, kallikrein, and Factor XIa. Factor XIa continues the coagulation pathway, kallikrein and Factor XIa convert plasminogen to plasmin and kallikrein digests HMW-kininogen to yield bradykinin. The Cl inhibitor, which inactivates Cls is the major plasma inhibitor of activated Hageman factor and kallikrein. In its absence, a potentially fatal form of angioedema is seen. The inactivator of the C3a and C5a anaphylatoxins is identical to carboxypeptidase N, the major plasma inactivator of bradykinin thus demonstrating the common control mechanisms which regulate the complement and kinin-forming pathways.
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PMID:The intrinsic coagulation-kinin pathway, complement cascades, plasma renin-angiotensin system, and their interrelationships. 704 77

A fragment of activated Hageman factor (HFf) has been demonstrated to activate the classical pathway of complement in a manner that is analogous to complement activation by antigen-antibody complexes or aggregated IgG. Thus C1, C4, C2, C3, and C5 were found to be depleted on addition of HFf to serum. The reduction of serum hemolytic activity was maximal upon addition of 5 micrograms HFf and an incubation time of 60 min at 37 degrees C. Consumption of the total complement activity and of the individual components proceeded in a dose-dependent fashion. No comparable activity was observed when equimolar concentrations of either the native Hageman factor (HF) or two-chain activated form of Hageman factor (HFa) were incubated with serum. Further, the ability of HFf to convert serum C3 and C4 was similar to that of aggregated IgG as assessed by immunoelectrophoresis. This function of HFf appeared to be independent of plasminogen (or plasmin) since plasminogen-free serum was indistinguishable from normal serum. Radial double immunodiffusion experiments using antiserum to C1q, C1r, and C1s on HFf-treated serum demonstrated the dissociation of the C1 trimolecular complex, with concomitant reduction of C1r antigenicity that is indicative of C1 activation. Thus, HFf appears to lead to C1 activation upon incubation with serum or when incubated with partially purified C1. This may represent a control link between activation of the intrinsic coagulation-kinin pathway and the initiation of the classical complement cascade.
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PMID:Activation of the classical pathway of complement by Hageman factor fragment. 725 10

Granulomas may be immunologically induced or non-immunologically induced. In immunologically induced granulomas cells of the monocyte-macrophage series take on the appearance of epitheloid cells. Ultrastructurally epithelioid cells may have a secretory appearance with much rough endoplasmic reticulum or take on highly degenerate vesicular appearance. Other epithelioid cells look like activated macrophages. Secretory epithelioid cells may be found associated with acute local inflammation as in borderline tuberculoid leprosy in reaction, the lepromin reaction, following injection of BCG vaccine and in experimental zirconium granulomas. In these situations there may also be strong histological and biochemical evidence of increased fibroblast activity and collagen synthesis. It is suggested that these cells are actively secreting a fibroblast-activating factor. Epithelioid cells may lose their Fc receptors, undifferentiated macrophages in lepromatous leprosy can lose their C3 receptors. It is suggested that in a number of situations granuloma formation may be associated with complement activation through the alternative pathway as in the case of mycobacterial granulomas. Toxic granulomas produced by metals may be caused by C3 being split by plasmin after conversion from plasminogen by activation of the Hageman factor.
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PMID:The monocyte-macrophage system in granulomatous inflammation. 732 27

Amyloid precursor protein forms that contain Kunitz protease inhibitor domains are released from activated platelets, T-lymphocytes, and leukocytes and inhibit trypsin, plasmin, and activated factor XI. We investigated the effects of amyloid precursor protein isoforms on activated Hageman factor (factor XII), activated factor X (Stuart factor), and thrombin. Recombinant amyloid precursor proteins with or without the Kunitz domain, 770 and 695 amino acids, respectively, were produced in insect cells by Baculovirus expression (BAC770 and BAC695). Neither BAC695 nor BAC770 inhibited human alpha-thrombin or activated factor X. The partial thromboplastin time was prolonged by both amyloid precursor proteins, only one of which, BAC770, contains the Kunitz protease inhibitor domain. Both forms of amyloid precursor proteins inhibited ellagic acid-induced activation of Hageman factor but did not inhibit activated Hageman factor. Bismuth subgallate, which is an insoluble analog of ellagic acid, lost its ability to activate Hageman factor on being exposed to BAC770. Inhibition of ellagic acid-induced activation of Hageman factor by both forms of amyloid precursor protein was enhanced by heparin. These findings suggested that the heparin-binding domain of amyloid precursor proteins is not in the Kunitz domain. This heparin-binding domain may block the activation of Hageman factor by negatively charged agents. Thus, amyloid precursor proteins may be involved in the control of hemostasis, properties not all dependent on the Kunitz domain.
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PMID:Inhibitory action of amyloid precursor protein against human Hageman factor (factor XII). 784 73

The fibrinolytic system was studied in normal human plasma containing increasing concentrations of acetone up to 23.4 mmol l-1. Fibrinolytic activity measured as euglobulin clot lysis time [ECLT] and amidase activities toward chromogenic peptide substrates H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide 2 HCl [S-2251], designed for plasmin determination, H-D-Valyl-L-Phenylalanyl-L-Lysine-p-nitroanilide 2 HCl [S-2390], designed for the determination of t-PA in plasma via plasminogen activation and H-D-Prolyl-L-Phenyl-Alanyl-L-Arginine-p-nitro-anilide 2 HCl [S-2302], designed for the determination of kallikrein and activated Hageman factor, increased when 15.7 mmol l-1 concentration of acetone was reached. A parallel increase of esterolytic [substrate: naphthol-AS-acetate] activity was observed in euglobulin fractions. Crossed immunoelectrophoresis [CIE] revealed changes in fibrinogen profiles of plasma enriched with acetone as compared to native plasma. These findings suggest that acetone present in plasma in concentrations comparable to those found in some pathological states might activate fibrinolytic system.
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PMID:Enhancement of fibrinolytic activity of human plasma in the presence of acetone. 799 40


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