Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombotic complications of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic system in blood, to the proteolytic enzyme plasmin. Plasmin dissolves the fibrin of a blood clot, but may also degrade normal components of the hemostatic system and predispose to bleeding. Currently, five thrombolytic agents are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction. These include streptokinase, urokinase, recombinant tissue-type plasminogen activator (rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC) and single chain urokinase-type plasminogen activator (scu-PA, prourokinase). The first generation thrombolytic agents, streptokinase (and probably also urokinase), are only moderately efficacious and their administration is associated with extensive systemic fibrinogen breakdown. In comparative studies performed in patients with acute myocardial infarction, recombinant tissue-type plasminogen activator (rt-PA) is a more effective and fibrin-specific thrombolytic agent than streptokinase. The acylated plasminogen streptokinase activator complex (APSAC) has a profile of thrombolytic efficacy and fibrin-specificity that is similar or somewhat better than that of streptokinase, but has the advantage that it can be administered by bolus injection. Single chain urokinase-type plasminogen activator is more fibrin-specific than urokinase. Comparative data on the efficacy and safety of this agent are limited as it is in the early stage of clinical investigation. Reduction of infarct size, preservation of ventricular function and/or reduction in mortality has been observed with streptokinase, rt-PA and APSAC. Therefore, thrombolytic therapy will probably become routine therapy for early acute myocardial infarction. In patients with acute myocardial infarction, intravenous streptokinase recanalizes 40-45 percent of occluded coronary arteries and reduces mortality by 25 percent; it costs approximately $200 for a therapeutic dose of 1,500,000 units. Recombinant tissue-type plasminogen activator (rt-PA) is more potent for coronary arterial thrombolysis, producing both more rapid and more frequent (65-70 percent) reperfusion, but it costs over $1,000 for a therapeutic dose of 100 mg. Side effects (mainly bleeding) and the incidence of reocclusion associated with the use of streptokinase and rt-PA are not markedly different. Whether the higher efficacy of rt-PA will translate into a comparably larger reduction of mortality remains to be determined in large comparative clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in thrombolytic therapy. 212 72

Plasminogen, plasmin, and plasminogen activator (PA) activities and PA and PA inhibitor (PAI) contents were measured in granulosa (GC) and theca interna cell extracts and follicular fluid (FF) obtained from preovulatory follicles of prepubertal gilts treated with eCG and hCG to induce follicular growth and ovulation. Plasmin activity in FF increased just before the time of expected ovulation. This increase was not attributable to changes in plasminogen levels, which remained relatively constant during preovulatory follicular development. The increase in follicular plasmin levels was associated with significant (p less than 0.01) increases in PA activity and content and decreases in PAI content in GC and FF. Western blot analysis suggested that follicular PA activity was represented principally by two forms of tissue type PA (t-PA) each with a pI of 7.8 and with molecular masses of 72,000 and 78,000 daltons, respectively. Two PA-PAI complexes of 126,000 and 130,000 daltons were observed. These complexes were partially dissociated with nucleophilic agents into two t-PA-like forms and a 52,000-dalton PAI protein with a pI of 4.8. Biochemical characteristics of the PAI protein suggest that it belongs to the same class of inhibitors as bovine and human PAI-1. These data indicate that rupture of the porcine ovarian follicle is temporally associated with a net increase in PA activity and an increase in plasmin activity. The increase in PA activity appears to be regulated by changes in PA and PAI content.
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PMID:Changes in and partial identification of the plasminogen activator and plasminogen activator inhibitor systems during ovarian follicular maturation in the pig. 214 59

Thrombotic complications of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic system in blood, to the proteolytic enzyme plasmin. Plasmin dissolves the fibrin of a blood clot, but may also degrade normal components of the hemostatic system and predispose to bleeding. Currently, five thrombolytic agents are either approved for clinical use or under clinical investigation in patients with acute myocardial infarction. These include streptokinase, urokinase, recombinant tissue-type plasminogen activator (rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC) and single chain urokinase-type plasminogen activator (scu-PA, prourokinase). The first generation thrombolytic agents, streptokinase (and probably also urokinase), are only moderately efficacious and their administration is associated with extensive systemic fibrinogen breakdown. In comparative studies performed in patients with acute myocardial infarction, recombinant tissue-type plasminogen activator (rt-PA) is a more effective and fibrin-specific thrombolytic agent than streptokinase. The acylated plasminogen streptokinase activator complex (APSAC) has a profile of thrombolytic efficacy and fibrin-specificity that is similar or somewhat better than that of streptokinase, but has the advantage that it can be administered by bolus injection. Single chain urokinase-type plasminogen activator is more fibrin-specific than urokinase. Comparative data on the efficacy and safety of this agent are limited as it is in the early stage of clinical investigation. Reduction of infarct size, preservation of ventricular function and/or reduction in mortality has been observed with streptokinase, rt-PA and APSAC. Therefore, thrombolytic therapy will probably become routine therapy for early acute myocardial infarction. In patients with acute myocardial infarction, intravenous streptokinase recanalizes 40-45 percent of occluded coronary arteries and reduces mortality by 25 percent; it costs approximately $200 for a therapeutic dose of 1,500,000 units. Recombinant tissue-type plasminogen activator (rt-PA) is more potent for coronary arterial thrombolysis, producing both more rapid and more frequent (65-70 percent) reperfusion, but it costs over $1,000 for a therapeutic dose of 100 mg. Side effects (mainly bleeding) and the incidence of reocclusion associated with the use of streptokinase and rt-PA are not markedly different. Whether the higher efficacy of rt-PA will translate into a comparably larger reduction of mortality remains to be determined in large comparative clinical trials. Both agents are available for clinical use.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in thrombolytic therapy. 218 Jan 14

The thrombolytic action of commercial plasmin-Fibrinolysin, heparin and complex Fibrinolysin-heparin in thecom bination with the alpha-adrenoceptor agent DET was studied in rats. The induction of venous thrombosis is accompanied by the manifestations of disseminated intravascular coagulation (DIC). The most efficient thrombolytic action in the hypercoagulemic stage of DIC had the complex Fibrinolysin-heparin in the combination with DET. The alpha-adrenoceptor antagonist blocked the compensatory reaction on plasmin excess, liberated vascular plasminogen activator and thus increased and prolonged thrombo- and fibrinolytic effects of this complex. Administration of this complex in the combination with DET resulted in a steady hypocoagulation and hyperfibrinolysis in blood stream.
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PMID:Use of alpha-adrenoceptor antagonist dihydroergotoxin in experimental anticoagulant and fibrinolytic therapy. 245 12

We present a cascade of proteolytic events catalyzed by the proteases secreted by cultured keratinocytes and fibroblasts that results in the activation of interstitial procollagenase. Cultured human skin fibroblasts constitutively secrete interstitial collagenase and stromelysin as proenzymes. In contrast, interstitial collagenase found in serum-free skin organ culture conditioned medium is activated. Cocultivation of the major cellular components of skin organ culture, dermal fibroblasts and epidermal keratinocytes, induces activation of interstitial procollagenase and prostromelysin in the presence of plasminogen. This activation occurs through a urokinase-dependent pathway where added keratinocytes secrete the plasminogen activator urokinase, which converts plasminogen into plasmin. Plasmin is capable of activating purified procollagenase and prostromelysin. Plasmin-dependent activation of procollagenase generates an enzyme species, by amino-terminal processing, identical to those generated by limited proteolysis with trypsin or treatment with organomercurial compounds. Catalytic amounts of activated stromelysin can in turn convert plasmin- or trypsin-activated collagenase into a fully active enzyme by removal of approximately 15 amino acid residues from the carboxyl end of the enzyme. This results in a 5- to 8-fold increase in collagenase specific activity that is due to its proteolytic cleavage and not to the presence of the activator stromelysin. Stromelysin alone in both pro- and activated forms is not capable of efficient activation of human fibroblast interstitial procollagenase.
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PMID:Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. 246 56

After incubation with human serum or plasma, 125I-basic fibroblast growth factor (bFGF) (molecular mass 18.5 kDa) exhibits molecular mass forms greater than 200 kDa as determined by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. These high molecular mass forms of bFGF are immunoprecipitable with antiserum raised against alpha 2-macroglobulin (alpha 2M). Purified alpha 2M and 125I-bFGF form a covalent complex in a specific, saturable manner. Excess unlabeled bFGF competes with 125I-bFGF for complex formation. Complex formation is complete after 4 h and is inhibited by pretreating alpha 2M with dithiothreitol, iodoacetamide, iodoacetic acid, and N-ethylmaleimide. The complex is resistant to acidic conditions and denaturants such as urea. Heparin, which binds bFGF, has no effect on complex formation. Methylamine, which blocks protease binding to alpha 2M, increases the amount of 125I-bFGF that can be bound 2-fold. Plasmin and trypsin treatment of alpha 2M has no effect on 125I-bFGF binding. The ability of growth factors to compete for binding is specific, as aFGF and TGF-beta compete for binding to alpha 2M, whereas platelet-derived growth factor does not. 125I-bFGF.alpha 2M complexes do not bind to low affinity bFGF binding sites and bind poorly to high affinity bFGF binding sites on BHK-21 cells. In addition, 125I-bFGF bound to alpha 2M has decreased ability to stimulate plasminogen activator production in bovine capillary epithelial cells.
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PMID:Alpha 2-macroglobulin is a binding protein for basic fibroblast growth factor. 246 67

The plasminogen activation system is quantitatively the major mechanism of extracellular proteolysis. To evaluate its role in retinal detachment, plasmin and plasminogen activators were measured in subretinal fluid (SRF) from 12 eyes of twelve patients. Plasmin was detected in 5 eyes (mean 6.26 micrograms/ml, SD = 3.7 micrograms/ml). Tissue-type plasminogen activator was present in 5 eyes (mean activity 0.33 IU/ml, SD = 0.24 IU/ml) but the activity did not associate with the plasmin activity in all of the SRF samples. Urokinase-type plasminogen activator was not detected in SRF. We conclude that the plasmin system has been activated in SRF in some eyes with retinal detachment with tissue-type plasminogen activator as the predominant activator. Plasmin in SRF may enhance dispersion of pigment epithelial cells into the subretinal space and the vitreous, a phenomenon seen frequently in eyes with retinal detachment.
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PMID:Tissue-type plasminogen activator in subretinal fluid. 252 85

The plasminogen activator activity (PAA) in extracts of the intima, media, and adventitia of the normal human aorta and other large arteries (carotid artery, renal artery and iliac artery) was studied with a sensitive, quantitative spectrophotometric assay using plasminogen and the chromogenic plasmin substrate S-2251. All layers of the arteries showed PAA which was highest in the adventitia, lowest in the media, while in the intima (aorta) PAA was intermediate, but much closer to that of the media. Plasminogen activator inhibition (PAI) was at the same level in all layers of the arteries studied. Plasmin inhibition (PI) was higher in adventitia than in intima (aorta), while in media the PI was intermediate. The PAA was due to the tissue-type plasminogen activator (t-PA), but not to the urokinase-type (u-PA), as judged by addition of respective antibodies. The relatively low PAA found in the intima of large arteries is therefore due to a low plasminogen activator and not a high plasminogen activator inhibitor activity or plasmin inhibitor level.
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PMID:Demonstration of plasminogen activator activity in the intima and media of the normal human aorta and other large arteries: immunological identification of the plasminogen activator(s). 252 44

A plasmin generation method to determine tissue plasminogen activator (t-PA) activity in plasma is described. A protein solution of homogenized fibrin was used as a stimulator in the presence of plasminogen and the plasmin generated was measured by the release of para-Nitroanilide (p-NA) from the chromogenic substrate S-2251. Plasmin generation by 5 iu/mL t-PA in the presence of 1 CU/mL of plasminogen and 850 micrograms/mL of fibrin solution reaches a peak at about 5 h incubation whilst in plasma, plasmin generation peaks after about 16 h incubation. The highest t-PA activity in plasma was determined using an assay involving 18 h incubation. In the 21 subjects studied by this method the t-PA activity at rest ranged from 0.34 to 0.92 iu/mL with a mean of 0.57 +/- 0.15 iu/mL of plasma whilst in the post-occlusion state the activity ranged from 1.12 to 18.0 iu/mL, with a mean of 5.25 +/- 4.49 iu/mL of plasma. We also found that subjects who developed petechiae during occlusion had significantly higher t-PA activity both at pre- and post-occlusion when compared with those who did not develop petechiae. The t-PA activity of acid-treated plasma stored at -70 degrees C showed no significant changes in activity after 12 weeks of storage when compared with the t-PA activity of the same plasma tested prior to storage.
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PMID:A plasmin generation method for the determination of tissue plasminogen activator (t-PA) activity in blood. 252 6

Plasminogen activator production by ovine embryos and the effects of plasminogen on ovine embryo development and zona pellucida integrity were evaluated. Eight-cell to sixteen-cell embryos were cultured in Whitten's medium containing 0, 60, or 120 micrograms/ml plasminogen. Plasmin and plasminogen activator concentrations in the medium were determined by a caseinolytic assay. More blastocysts hatched in medium containing 60 and 120 micrograms/ml plasminogen (33 and 21%, respectively) than 0 microgram/ml plasminogen (0%; p less than 0.05). Zona pellucida dissolution time in acidified phosphate-buffered saline was less after incubation in medium with 60 and 120 micrograms/ml plasminogen (7.2 and 5.9 min, respectively) than 0 microgram/ml plasminogen (9.4 min; p less than 0.05). Plasminogen activator production was low until the morula stage, increased during morula-blastocyst transition, and remained elevated through blastocoelic expansion and hatching. Zona pellucida solubility, plasminogen activator production, and plasminogen conversion to plasmin increased as embryonic stage advanced; however, plasminogen activator production and plasmin conversion to plasmin were poorly correlated with zona pellucida solubility. The results indicate that ovine embryos produce plasminogen activator, and plasmin can increase zona pellucida solubility; however, other factors may also be involved in altering zona pellucida integrity prior to hatching.
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PMID:The effects of plasminogen on in vitro ovine embryo development. 253 79


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