Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Newborn rat cerebellum microexplants cultured in Minimal Essential Medium with glucose and insulin released plasminogen activator (PA), which was detected in living cultures by a substrate overlay assay. Gel electrophoresis of cerebellum-conditioned medium followed by zymography resolved PA activity in two separate bands of 48,000 and 75,000 daltons apparent mol. wt. Using specific antisera, these bands were shown to be respectively urokinase and tissue-type PA. Cerebellum conditioned medium as well as purified human urokinase induced the proliferation and outgrowth of glial fibrillary acid protein-positive cells from newborn cerebellar microexplants. The effect was suppressed by the serine protease inhibitor phenyl methanesulfonylfluoride. Since PAs are most likely of neuronal origin, we suggest that at least one of these proteases acts as a neuronoglial mitogenic signal during development.
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PMID:Plasminogen activator is a mitogen for astrocytes in developing cerebellum. 403 64

1. The cytokinase (tissue activator of plasminogen) content of several mammalian tissues was evaluated by a quantitative casein hydrolysis method. 2. An alkaline (pH10.5) extraction of cytokinase from rabbit kidney lysosome-microsome fraction, followed by chromatography on DEAE-cellulose at pH7.6 with stepwise or linear increase in concentration of phosphate buffer, gave an 86-fold purification of the enzyme. The purified material was non-proteolytic against casein and heated fibrin and was freeze-dried without significant loss of activity or solubility. 3. Cytokinase is a protein with E(0.1%) (1cm.)=0.87 at 280mmu, and does not possess sufficient hexose or sialic acid to be classified as a glycoprotein. It has S(20,w) 2.9-3.1s and molecular weight 50000 when measured on a calibrated Sephadex G-100 column. It has an isoelectric point between pH8 and pH9, and is maximally active and stable at pH8.5. It is inactivated by heat at 78 degrees . 4. Cytokinase and human urokinase have the same K(m) value and are inhibited in a partially competitive manner by in-aminohexanoic acid and aminomethylcyclohexanecarboxylic acid. They are also inhibited by cysteine and arginine, but are unaffected by iodoacetamide and p-chloromercuribenzoate. 5. On the basis of this and other evidence it is suggested that rabbit kidney cytokinase and human urokinase are similar, if not identical, enzymes.
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PMID:Purification of rabbit kidney cytokinase and a comparison of its properties with human urokinase. 564 83

Coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) were performed in 32 patients with evolving acute myocardial infarction. Of the 25 patients with complete occlusion of an infarct-related coronary artery, in 18 (72%) the occluded vessel was successfully opened by an intracoronary infusion of urokinase. With a small dose of urokinase the successful recanalization was achieved in only 25%; with a larger dose it was achieved in 94%. After PTCA, all patients received glucose-insulin-potassium solution for 76 hours. Repeat angiography 42 days later showed a patent coronary artery in 12 (group A) of 18 patients with successful PTCA. In group A, left ventricular ejection fraction increased from 51 +/- 13% to 72 +/- 10% (p less than 0.01) and regional wall shortening from 4.5 +/- 9.5% to 29 +/- 19% (p less than 0.01). In contrast, these variables did not change significantly in patients with unsuccessful PTCA or late reocclusion of an infarct-related vessel (group B). These data suggest that successful PTCA with sustained patency of an infarct-related coronary artery has a beneficial effect on the salvage of the jeopardized myocardium, and glucose-insulin-potassium therapy may enhance the beneficial effect of PTCA.
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PMID:Effects of percutaneous transluminal coronary angioplasty: intracoronary thrombolysis with urokinase in acute myocardial infarction. 623 47

Fibrinolytic treatment of acute myocardial infarction with streptokinase and urokinase has now been under investigation for almost 20 years. Initially encouraging reports of beneficial effects of streptokinase were not substantiated by carefully controlled studies performed on coronary care and intensive care units. Studies carried out during the last tne years were characterized by non-uniform trial conditions and results. Similarly, to date no clearly beneficial effects of urokinase could be established. In order to provide more concise analysis, the "European Cooperative Study Group for Streptokinase Treatment in Myocardial Infarction" conducted a multi-center controlled trial. Patients were allocated to risk-groups. Three-hundred fifteen patients with medium and high risk were randomized to a 24-hour infusion of streptokinase or glucose. The overall mortality within six months was significantly lower in the streptokinase group (p less than 0.01) contributed primarily by eight of the eleven centers. Only 13.5% of patients with myocardial infarction, however, were eligible for the study. Interpretation of the results yielded no indication of the nature of the fibrinolytic effects nor how the benefit could be explained pathophysiologically. Furthermore, it remains questionable whether systemically-administered streptokinase can lyse coronary thrombosis or reduce the size of myocardial necrosis. An indirect effect of streptokinase through lowering of blood viscosity and subsequently, peripheral capillary resistance may represent a theoretical possibility. the indication of routine systemic administration of streptokinase has not yet been established. Recent reports of promising results obtained by direct, intracoronary infusion of thrombolytic agents indicate that this alternative may lead to realization of a specific effect in reduction of coronary thrombosis and, consequently, myocardial necrosis.
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PMID:[Fibrinolytic treatment of acute myocardial infarction (author's transl)]. 721 22

The immobilization of some medically useful enzymes were studied by means of radiation-induced polymerization at -78 degrees C. Glucose oxidase and glucose peroxidase were immobilized in the form of thin membranes inside polyvinyl chloride tubes and on polyethylene films; these membranes showed considerable activity yield, as well as good activity retention. Two effective methods were adopted to improve the surface properties of the base materials and to facilitate firm immobilization by coating: that is, an undercoating method followed by radiation curing of the undercoating and an irradiation grafting method with a monomer. Both were tested with good results. An immobilization of urokinase was also carried out successfully by similar methods. The thrombogenicity of the immobilized urokinase showed a remarkable effect on thombus formation.
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PMID:Immobilization of enzymes for medical uses on plastic surfaces by radiation-induced polymerization at low temperatures. 736 85

Patients with diabetes are predisposed to microvascular disease. In the retina and brain, this is characterized by neovascularization and new capillary formation. Because of the potential importance of plasmin generation in these processes, we evaluated the effect of elevated glucose concentrations on expression of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and urokinase (uPA) in cultured bovine brain endothelial cells (BBEC) versus cultured bovine aortic endothelial cells (BAEC). We observed that BBEC PAI-1 mRNA levels were decreased fivefold in cells cultured in media containing 20 mM glucose compared with BBEC cultured in media with 5.5 mM glucose, whereas expression of PAI-1 mRNA in BAEC, bovine mesenteric endothelial cells, and human umbilical vein endothelial cells was not modulated under these conditions. Expression of PAI-1 protein was also inhibited by growth of BBEC in elevated glucose, but the effect was less marked than at the mRNA level. Elevated glucose did not decrease expression of PAI-1 protein by BAEC. Withdrawal of acidic fibroblast growth factor enhanced expression of PAI-1 mRNA and protein in BBEC. Expression of tPA mRNA was not affected by the glucose concentration of the medium, and uPA mRNA was not detected in our BBEC cultures. A decrease in the local tissue activity of PAI-1 by elevated glucose concentrations, with no effect on tPA or uPA expression, would lead to an increase in the plasmin activity and thereby predispose neural tissues, such as the cerebrum and retina, of diabetic patients to neovascularization.
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PMID:Plasminogen activator inhibitor-1 expression by brain microvessel endothelial cells is inhibited by elevated glucose. 751 64

We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low-potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors. 777 33

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.
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PMID:A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells. 792 84

We studied urokinase-type plasminogen activator (u-PA)-dependent chemotaxis and DNA synthesis in both human fibroblasts and LB6 mouse fibroblasts transfected with human u-PA receptor (u-PAR) gene (LB6 clone 19). Both cell lines have receptors for the amino-terminal fragment of u-PA (u-PA-ATF). We observed that u-PA and u-PA-ATF stimulated chemotactic migration of both LB6 clone 19 cells and human fibroblasts, which could be impaired by down-regulation of protein kinase C (PKC) with phorbol myristate acetate (PMA). While LB6 clone 19 cells were unable to undergo mitosis following exposure to either u-PA or u-PA-ATF, human fibroblasts were stimulated to mitosis by exogenous addition of native u-PA, and u-PA-ATF was ineffective. The mitogenic activity of u-PA on human fibroblasts could also be impaired by down-regulation of PKC with PMA. We studied second messenger formation following u-PAR stimulation. Neither inositol lipid metabolism nor intracellular Ca2+ content were affected, while an increase of diacylglycerol (DAG) generation was observed. Such DAG formation was related to de novo synthesis from glucose and was dependent on ligand-receptor interaction. Both u-PA-ATF and the native u-PA molecule were able to stimulate DAG formation, u-PA being from three to fourfold more efficient than ATF. These data suggest that u-PAR stimulation per se is sufficient to trigger DAG formation. The native molecule confers on the cell an additional stimulus, possibly related with the activation of a u-PA-catalytic site-dependent substrate. Such stimulation allows the cell to reach the DAG threshold level required to trigger DNA synthesis.
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PMID:Production of second messengers following chemotactic and mitogenic urokinase-receptor interaction in human fibroblasts and mouse fibroblasts transfected with human urokinase receptor. 805 May 1

The genes coding for glucose regulated protein, 78kDal (GRP78), hormone-sensitive lipase (LIPE), plasminogen activator or urokinase (PLAU), and D-amino acid oxidase (DAO) were localized in the pig by radioactive in situ hybridization. GRP78 was mapped to 1q2.10-->q2.13 and LIPE was localized to chromosome 6cen-->q1.2. The genes for PLAU and DAO were both assigned to chromosome 14, in the region q2.4-->q2.6 and q2.1-->q2.3, respectively. The results are compared to mapping data in other mammalian species.
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PMID:Localization of four new markers to pig chromosomes 1, 6, and 14 by radioactive in situ hybridization. 810 65


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