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)

As observed for many proteins, glucose has been shown to bind non enzymatically to fibrinogen and to fibrin. The in vitro degree of glycosylation depends upon the concentration of glucose added to fibrinogen and also on the incubation period. This glycosylation induces a decrease in fibrin lysis by plasmin. On the contrary, it does not influence either fibrinogen activity as cofactor in ADP-induced platelet aggregation or the binding of thrombin onto a clot. Despite the 4 day half life of fibrinogen, since clearance of fibrinogen is exponential, it is assumed that very small quantities of fibrinogen may remain for a long time in the circulation leading to the presence of a low level of a highly glycosylated form of fibrinogen. Consequently, poorly degradable fibrin might be derived from this highly glycosylated fibrinogen and thus be responsible for capillary occlusion and also for atherosclerotic complications in the diabetic patient.
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PMID:Glycosylation of human fibrinogen and fibrin in vitro. Its consequences on the properties of fibrin(ogen). 312 89

We have studied the effect of streptokinase on platelets in platelet-rich plasma (PRP) and of plasmin on washed platelets. By three and one-half minutes after the addition of 50,000 IU/mL streptokinase to PRP, the maximum rate of ristocetin-induced platelet agglutination declined 40%, and by 60 minutes, it declined 70%. During the same time interval, the thrombin time increased from 20 seconds to over 120 seconds. At a concentration as low as 50 IU/mL, streptokinase reduced the maximum rate of ristocetin-induced platelet agglutination by 50% and prolonged the thrombin time to 1.5 times control value. Streptokinase added to PRP also caused inhibition of platelet aggregation following stimulation by 2.9 mumol/L adenosine diphosphate, 0.25 U/mL thrombin, and 0.025 mg/mL collagen. Plasmin, 0.05 to 1.0 CU/mL, reduced ristocetin-mediated agglutination of washed platelets in the presence of von Willebrand factor (vWF) from 66% of control to 2% of control, following a one-hour incubation. Autoradiograms produced following sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) of plasmin-treated 125I-surface-labeled platelets demonstrated progressive loss of a protein with a molecular weight (mol wt) of 180,000; simultaneously, a protein with mol wt 135,000 appeared on autoradiograms produced following SDS-PAGE of the surrounding platelet medium. These proteins are similar in molecular weight to glycoprotein (gp) Ib, a platelet surface receptor for vWF, and glycocalicin, a proteolytic fragment of gpIb. By use of an enzyme-linked immunosorbent assay (ELISA) based immunoinhibition assay for glycocalicin, we were able to demonstrate that plasmin treatment of washed platelets released a glycocalicin-related antigen into the surrounding medium and that appearance of this material corresponding to loss of vWF-dependent, ristocetin-induced agglutination.
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PMID:Plasmin effect on platelet glycoprotein Ib-von Willebrand factor interactions. 315 89

The effects of plasmin have been examined because platelets may be exposed to plasmin in vivo and treatment of platelets with plasmin shortens platelet survival. Rabbit plasmin was prepared by urokinase activation of plasminogen immobilized on lysine-Sepharose. Plasmin caused rabbit platelets to aggregate and release the contents of their amine storage granules, but aggregation was slower than in response to ADP or thrombin. EDTA, prostaglandin E1, or creatine phosphate/creatine phosphokinase were inhibitory, but indomethacin was not. Deaggregation did not occur when platelets had been aggregated by a concentration of plasmin that caused extensive release of granule contents. EDTA or prostaglandin E1 caused deaggregation. Low concentrations of ADP and plasmin acted synergistically in causing platelet aggregation. Plasmin decreased the amounts of platelet membrane glycoproteins that stained with periodic acid-Schiff reagent; glycoprotein I was more susceptible than glycoprotein II and III. Concentrations of plasmin that induced the release of amine storage granule contents also released PAS-staining granule glycoproteins. Platelets incubated with plasmin, washed and resuspended, were not aggregated by ADP, but were aggregated strongly by the combination of fibrinogen and ADP, and bound 125I-fibrinogen to a greater extent than untreated platelets. Platelets preincubated with a high concentration of plasmin were unresponsive to thrombin, but were sometimes aggregated by fibrinogen. Plasmin decreased the buoyant density and increased the median size of platelets. Thus plasmin, as well as ADP and thrombin, may contribute to the density shift observed in platelets from rabbits in which thrombosis and continuous vessel injury have been induced.
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PMID:Effects of plasmin on rabbit platelets. 315 94

The progressive stabilization of fibrinogen binding to ADP-treated platelets has been well described, but the nature of this interaction remains obscure. In the present study, irreversibly bound fibrinogen was defined as that fraction of bound iodinated fibrinogen that failed to dissociate from stimulated human gel-filtered platelets within 10 min of adding 10 mM ethylenediaminetetraacetic acid. It represented 16 +/- 11% (mean +/- SD, n = 10) of fibrinogen bound to ADP-treated platelets after 1 min and 52 +/- 11% of fibrinogen bound to these platelets after 60 min. Similar results were obtained if platelets were stimulated with purified human thrombin (0.1 U/ml) or epinephrine (10 microM). Irreversible fibrinogen binding was significantly reduced at 4 degrees C (27 +/- 9%, mean +/- SD, n = 6) if platelets were preincubated (30 min, 25 degrees C) with 30 micrograms/ml cytochalasin B or D (18 +/- 8%) or stimulated with chymotrypsin (0.5 mg/2-3 X 10(8) platelets) (31 +/- 8%). Formation of irreversible platelet-fibrinogen interactions correlated with the incorporation of actin and actin-binding protein into the Triton X-100-insoluble platelet cytoskeleton and the ability of platelets to retract fibrin clots. Irreversibly bound fibrinogen was available on platelets for digestion by 0.2 U/ml plasmin. The enzyme removed 96 +/- 6% (mean +/- SD, n = 6) of all bound fibrinogen from platelets after 30 min at 25 degrees C. This was not accompanied by significant release of [14C]serotonin or lactate dehydrogenase. Furthermore, platelets incubated with plasmin could bind fibrinogen normally after the enzyme had been neutralized with aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Examination of irreversible platelet-fibrinogen interactions. 315 13

In a proposed study of fibrinolytic therapy in experimental streptococcal endocarditis, this disease was induced in pigs by preinoculation damage to the aortic valve; the technique of this is described. If untreated, the disease runs a protracted course, similar to that in man. Fibrinolytic activity, normally low in the pig, can be increased by stress, by urokinase, by plasmin and briefly by streptokinase if supplemented by human plasminogen. The proposed experiments were abandoned in pigs, chiefly because of technical difficulties in obtaining frequent samples of blood and maintaining infusions. In experiments on the response of ADP-induced aggregation of pig platelets to prostacyclin, they were found to be about 10 times more resistant than human platelets. It is suggested that this resistance to prostacyclin, together with their usually low state of systemic fibrinolytic activity, may explain the susceptibility of pigs to bacterial endocarditis.
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PMID:A study of experimental endocarditis in pigs. 331 15

A mechanism by which platelets might participate in fibrinolysis by binding plasminogen and influencing its activation has been examined. Binding of radioiodinated human Glu-plasminogen to washed human platelets was time-dependent and was enhanced 3-9-fold by stimulation of platelets with thrombin but not with ADP. The interaction with both stimulated and unstimulated cells was specific, saturable, divalent ion-independent, and reversible. The platelet-bound ligand had the molecular weight of plasminogen, and no conversion to plasmin was detected. Scatchard analyses provided evidence for a single class of plasminogen-binding sites on both stimulated and unstimulated cells. The Kd for thrombin-stimulated platelets was 2.6 +/- 1.3 microM, and 190,000 +/- 45,000 molecules were bound per cell, whereas unstimulated platelets bound 37,000 +/- 10,500 molecules/cell with a Kd of 1.9 +/- 0.15 microM. Plasminogen binding was inhibited in a dose-dependent manner by omega-aminocarboxylic acids at concentrations consistent with a requirement for an unoccupied high affinity lysine-binding site for plasminogen binding to the cells. When platelet-bound plasminogen was incubated with tissue plasminogen activator, urokinase, or streptokinase, gel analysis established that plasmin was preferentially associated with the platelet relative to the supernatant. Plasminogen and plasmin interacted with thrombin-stimulated platelets with similar binding characteristics, and there was no evidence for a binding site for plasmin which did not also bind plasminogen. Therefore, the results suggest that plasminogen activation is enhanced on the cell surface. In sum, these results indicate that platelets bind plasminogen at physiologic zymogen concentrations and this interaction may serve to localize and promote plasminogen activation.
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PMID:Binding and activation of plasminogen on the platelet surface. 392 Feb 16

Two polypeptides of 74 kDa and 55 kDa have been isolated from human platelets by immunoaffinity and lectin affinity chromatography and their effects on thrombin reactivity have been examined. These proteins in combination enhanced the aggregation of platelets by thrombin while aggregation induced by trypsin, collagen and adenosine diphosphate was not significantly affected. An enhancement in the action of thrombin on fibrinogen, N-benzoylarginine ethyl ester and H-D-phenylalanyl-L-pipecolyl-L-arginine-p-nitroanilide dihydrochloride was also observed in the presence of the platelet proteins. Under similar conditions, the proteins did not influence the esterolytic activity of trypsin or plasmin. Studies at different thrombin and protein concentrations showed maximum enhancement of enzyme reactivity when the ratio between the peptides and thrombin was optimal. In the presence of these proteins, the affinity of thrombin for N-benzoylarginine ethyl ester was about twofold higher than in the control. Two polypeptides with properties similar to those described above have also been isolated from human plasma. Antibodies to the above proteins isolated from either platelets or plasma were raised in rabbits. Intact platelets solubilized in Triton X-100 or plasma showed two precipitin lines in immunoelectrophoresis against both of the above antisera and a similar pattern was observed with the isolated polypeptides. The polypeptides did not interact in immunoelectrophoresis with antisera to whole serum, antithrombin, C4 binding protein or protein S. These 74-kDa and 55-kDa polypeptides contained radioactivity when radioiodinated platelets were used suggesting that they are located on the cell surface. Fresh plasma was analyzed by gel electrophoresis under nondenaturing and denaturing conditions and the proteins were transferred to nitrocellulose sheets. Staining with antibody to these thrombin-reactive proteins and 125I-protein A showed several reactive plasma proteins under nondenaturing conditions with the major band migrating in the albumin area. In plasma treated with sodium dodecyl sulfate, the 74-kDa and 55-kDa components were observed. A prominent 74-kDa band and a fainter 55-kDa component were again observed when platelets solubilized in sodium dodecyl sulfate were analysed by the above procedure. It is proposed that human platelets and plasma contain polypeptides which may directly modulate thrombin reactivity.
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PMID:Thrombin-reactive polypeptides of human blood. Some biochemical and immunological properties. 400 39

The venom of the rhinoceros horned viper (Bitis nasicornis) has been studied in vitro and has been shown to be anticoagulant. This action appeared to be due to an effect on both the extrinsic and intrinsic blood thromboplastin mechanisms. The venom was also proteolytic and in purified caseinolytic systems activated plasminogen, enhanced the activation of plasminogen by streptokinase, and potentiated the action of plasmin. In the euglobulin clot lysis system high concentrations of venom produced inhibition. The crude venom increased platelet adhesiveness but in high concentrations delayed the snowstorm effect in the Chandler's tube system and inhibited platelet adenosine diphosphate reactivity. Passage through carboxymethylcellulose yielded six fractions. One possessed anticoagulant activity, inhibited plasmin, and increased the optical density of platelet-rich plasma. The other five fractions shortened the plasma recalcification time but had no effect on plasmin activity. Four fractions aggregated platelets and enhanced platelet adenosine diphosphate reactivity.
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PMID:Effects of the venom of the rhinoceros horned viper (Bitis nasicornis) on blood coagulation, platelet aggregation, and fibrinolysis. 425 26

Trypsin-activated pig plasmin and human plasmin activated by streptokinase (SK) caused aggregation of a suspension of washed platelets from human, rabbit, or pig blood. The platelet aggregation was reversible, but it was accompanied by a significant release of adenine nucleotides, serotonin, and platelet fibrinogen. Platelet fibrinogen was eventually digested. The effect of plasmin on platelets was inhibited by soybean trypsin inhibitor, epsilon aminocaproic acid, Persantin, prostaglandin E(1), and phenylbutazone. Short treatment of platelets with plasmin enhanced their sensitivity to ADP; however, this sensitivity was lost during longer incubation with plasmin. This enzyme also made platelets less sensitive to collagen and thrombin. Injecting SK into rabbits (10,000 U/kg body weight) caused a transitory drop of platelet count. These platelets lost part of their serotonin and fibrinogen. The administration of Persantin or of epsilon aminocaproic acid to rabbits before the injection of SK protected platelets from the loss of serotonin. Pretreatment with Persantin also resulted in partial protection of platelet fibrinogen in rabbits injected with SK. Platelets obtained from rabbits that had received both Persantin and SK were much more reactive with collagen than platelets obtained from rabbits injected with SK alone. Rabbits pretreated with Persantin did not show prolongation of the primary bleeding time that occurred after SK injection to control rabbits. It is suggested that plasmin generated after SK injection causes platelet release reaction in vivo. This may contribute to the hemostatic defect occurring during thrombolytic therapy or during systemic activation of fibrinolysis due to the other factors.
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PMID:Plasmin-induced platelet aggregation and platelet release reaction. Effects on hemostasis. 426 96

The effects of the venoms of Naja melanoleuca, Naja nigricollis, and Ophiophagus hannah on blood coagulation, platelet aggregation, and fibrinolysis were studied in vitro. All three venoms were shown to be anticoagulant. This action appeared to be due to an effect on both the extrinsic and blood thromboplastin mechanisms. Platelet aggregation in Chandler's tubes and adenosine diphosphate reactivity were inhibited by the three venoms, although in the case of Ophiophagus hannah venom they were inhibited only with intermediate concentrations. The three venoms possessed proteolytic properties, but when incorporated into purified caseinolytic systems and euglobulin clot lysis systems inhibition of plasmin activity was observed.
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PMID:Effects of three cobra venoms on blood coagulation, platelet aggregation, and fibrinolysis. 581 35


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