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)

Plasminogen activity and antigen, tissue-type plasminogen activator (tPA) activity and antigen, plasminogen activator inhibitor (PAI) activity, and plasmin generation rates were determined in 32 normal newborn plasmas and 25 normal adult plasmas. The newborns showed reduced levels of plasminogen activity and antigen and tPA antigen, and activity, normal levels of PAI activity, and slower plasmin generation rates. The slower generation was shown to be due to the hypoplasminogenemia. The in vitro plasmin generation studies also showed that the newborn needed 11 times the usual concentration of urokinase and 5 times the usual concentration of tPA to achieve the minimal activation rate of the adult.
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PMID:Newborn's fibrinolytic mechanism: components and plasmin generation. 253 Aug 97

The expression of the plasminogen activator, urokinase, and the display of its receptor in response to growth factors were examined in a serum-free adapted colon cancer cell line, CBSsf. Cells propagated in protein-free medium secreted 6.5 +/- 1.0 ng/ml of urokinase/10(6) cells in a 3-day period as determined by enzyme-linked immunosorbent assay. Inclusion of insulin or transferrin into the protein-free medium was without effect on this parameter. However, addition of epidermal growth factor (EGF) to the protein-free medium resulted in a 50% reduction in this parameter. This change was also reflected in the plasminogen-dependent solubilization of immobilized radioactive laminin. Plasminogen-supplemented conditioned medium derived from CBSsf cells grown in protein-free medium solubilized 135,000 +/- 25,000 dpm/10(6) cells of radioactive substrate. This value was decreased to 59,000 +/- 6,000 when conditioned medium was collected in the presence of EGF. Dose-response curves indicated that, while 0.5 ng/ml of EGF were suboptimal for the suppression of urokinase secretion, a concentration of 5.0 ng/ml had a maximum effect on this measurement. Northern hybridization studies indicated that the reduced plasminogen activator reflected, at least in part, translation of a less abundant transcript. Examination of the colon carcinoma cell line for altered urokinase receptor display revealed that EGF caused a dose-dependent increase in the amount of radioactive urokinase bound. This did not reflect reduced occupation of binding sites with endogenous ligand. Scatchard manipulation of the binding data indicated that the increased amount of radioactive plasminogen activator bound to cells cultured with EGF reflected an increase in receptor number from 7,500 to 13,000 sites/cell. Time course studies revealed that the decrease in urokinase secretion precedes changes in receptor display by 5 h. A 60% reduction in assayable urokinase was demonstrated in the conditioned medium from cells treated with the growth peptide for 10 h. However, a 24-h period was required to observe an increase (80%) in the amount of radioligand bound to EGF-treated cells. These data suggest EGF to be a regulator of both urokinase production and urokinase receptor display in a colon cancer cell line.
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PMID:Examination of the effects of epidermal growth factor on the production of urokinase and the expression of the plasminogen activator receptor in a human colon cancer cell line. 253 3

The relevance of urokinase receptors to urokinase-mediated laminin degradation was investigated in cultured colon cancer. Six colon cancer cell lines degraded laminin in a plasminogen-dependent manner. The ability of the individual cell lines to cleave the glycoprotein correlated well (r2 = 0.9242) with the amount of urokinase recovered from the cell surface by a mild acid treatment. A radioreceptor assay indicated that colon cancer cells most active in degrading the laminin, possessed the largest number of urokinase receptors. Moreover, acid treatment which depletes the receptors of endogenous plasminogen activator augmented the specific binding of radioactive urokinase to the colon cancer cells by 12-200%. A cell line (HCT 116) which displayed 1.1 x 10(5) receptors/cell the majority of which were occupied with endogenous urokinase was selected and the effects of a urokinase receptor antagonist on laminin degradation determined. The peptide antagonist reduced laminin turnover by 60-80%. Morphological observations were consistent with these findings. Plasminogen-treated HCT 116 cells retracted from the culture dish and many cells were observed in the culture medium. This effect could be largely reversed by simultaneous treatment with the peptide antagonist. A poor correlation was found between laminin degradation and soluble urokinase (r2 = 0.1074). These data strongly argue for a role of the urokinase receptor in facilitating the action of the plasminogen activator in colon cancer.
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PMID:Examination of the role of the urokinase receptor in human colon cancer mediated laminin degradation. 255 98

To understand the mechanisms regulating osteoid removal by osteoblasts, mouse calvarial osteoblasts were grown on 14C-labelled type I collagen films and stimulated with 1,25-dihydroxyvitamin D-3 (2.5.10(-8) M) for 48-72 h. In the presence of 5% non-inhibitory rabbit serum this resulted in a 2-3-fold increase in collagen degradation and a dramatic change in osteoblast morphology, when compared with untreated osteoblasts. Collagenolysis was accompanied by increased synthesis and release of latent collagenase, gelatinase and stromelysin and a concomitant decrease in their specific inhibitor, TIMP (tissue inhibitor of metalloproteinases). In serum-free medium, osteoblasts failed to degrade collagen, but their ability to lyse collagen could be restored by adding plasminogen (5 micrograms/ml) to the cultures. Plasminogen-dependent collagenolysis was inhibited by human recombinant TIMP (5 units/ml), demonstrating that plasmin, derived from plasminogen, activated latent collagenase and did not itself degrade collagen. Plasminogen activator production was confirmed by culturing osteoblasts on 125I-labelled fibrin plates. Comparison with urokinase-type and tissue-type plasminogen activator standards suggested that osteoblast plasminogen activator was predominantly cell-associated and likely to be of the urokinase type. Immunocytochemistry indicated that osteoblasts also constitutively produce plasminogen activator inhibitor-1. These findings provide evidence for the involvement of a plasminogen-plasmin-latent metalloproteinase activation cascade in type I collagen degradation by osteoblasts, and for its regulation by TIMP and plasminogen activator inhibitor-1.
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PMID:Type I collagen degradation by mouse calvarial osteoblasts stimulated with 1,25-dihydroxyvitamin D-3: evidence for a plasminogen-plasmin-metalloproteinase activation cascade. 255 72

Plasminogen activator activity and plasmin-like amidolytic activity were investigated in two experimental rat tumours, using human plasminogen and chromogenic peptide substrate, S-2251. The invasive hepatocarcinoma and non-invasive nephroma were induced with the same chemical carcinogen, dimethylnitrosamine, in F-344 rats and they were continuously transplanted under the renal capsule. While there was no difference in plasmin-like activities of the tumours, the plasminogen activator activity was very low in the nephroma, but high in the hepatocarcinoma. Since the activator activity was completely inhibited by amiloride, it was considered to be of urokinase-type. These results were in accordance with the assumed role of urokinase in the invasion. However, of the respective control organ, kidney was rich in both activities but rat liver contained only very low activities. Therefore the comparison of the plasminogen activator activity of a tumour to the control organ probably does not provide information concerning the malignant transformation as it is suggested in the literature.
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PMID:Plasminogen activator and plasmin-like activities in experimental rat tumours. 255 73

Plasminogen activators have been implicated in the process of tumour growth, invasion and metastatic spread. Recent studies indicate that urokinase (mu-PA) is the major type of plasminogen activator correlated with the evolution of adenocarcinomas of the colon. Comparable changes in the plasminogen activator profile have been found in premalignant conditions of the colon as observed in adenocarcinomas. The feasibility of determining plasminogen activators in endoscopical biopsies may provide diagnostic opportunities for the detection of early malignant changes in the human colon.
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PMID:Plasminogen activators in (pre)malignant conditions of the colorectum. 264 80

Plasminogen activators of distinct structure and biochemical action seem to be more equivalent than unique regarding induced blood changes and clinical complications. All of the activators ultimately degrade substrate through plasmin, resulting in a striking hypocoagulable state characterized primarily by a decrease in fibrinogen concentration. Infusion regimens are inversely proportional to the half-life of the activator, which is relatively long with anisoylated plasminogen streptokinase activator complex (APSAC), intermediate for streptokinase (SK) and urokinase (UK), and very short for recombinant tissue plasminogen activator (rt-PA) and recombinant single-chain urokinase plasminogen activator (scu-PA). After therapy is discontinued, hypofibrinogenemia persists until activator is cleared from the blood, then is slowly corrected over 48 hours, regardless of which thrombolytic agent has been used. Coagulation and platelet activity may be transiently accentuated soon after administration of the agent. Hypercoagulability contributes to vascular reocclusion, especially when acting in concert with the thrombogenic influences of residual thrombus and the original ruptured atherosclerotic plaque. In the first 3 to 4 hours after symptom onset, coronary artery reperfusion can be achieved with all of the thrombolytic agents in 50 to 60% of patients, with a greater thrombolytic potential of rt-PA over SK in thrombi of greater than 4 hours' duration. After coronary artery reperfusion, reocclusion occurs in 10 to 20% of patients, more often after rt-PA than SK treatment. Antiplatelet agents such as aspirin decrease the incidence of reocclusion and when added to either SK or rt-PA, decrease mortality after acute myocardial infarction by half. APSAC appears to have a maximal beneficial effect in reducing mortality even without aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of thrombolytic agents: selected hematologic, vascular and clinical events. 266 39

Plasminogen activators initiate the fibrinolytic system by conversion of the proenzyme plasminogen to the active fibrin degrading enzyme plasmin. Plasminogen activator inhibitors inhibit the effects of both plasminogen activators. Uncomplicated pregnancies are accompanied by hypercoagulability and an increased risk of thromboembolic disease. Thrombosis is rare in the first trimester and most events are noted in the last trimester. Therefore, we studied the fibrinolytic system at the end of pregnancy and in the puerperium. Plasma concentrations of urokinase plasminogen activator (u-PA/competitive radioimmunoassay), tissue type plasminogen activator (t-PA/sandwich ELISA) and plasminogen activator inhibitor (PAI/functional assay) were determined in 44 women (age: 24.3 +/- 4.3 years) with normal pregnancy near term. Plasma samples were collected before the onset of labour and 1, 2, 3, 4 and 5 days after delivery. Compared with an age-matched non pregnant control group (8.3 +/- 3.94 U/ml) significantly increased PAI activity (12.13 +/- 4.79 U/ml - p less than 0.005) was measured before delivery with a subsequent significant decrease (8.13 +/- 1.97 U/ml) to normal values on day 1 after delivery; plasma u-PA and t-PA antigen levels remained unchanged. Placental weight and birth weight had no influence on plasma levels of both plasminogen activators.
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PMID:Influence of delivery on plasminogen activator inhibitor activity. 268 64

Plasma concentrations of plasminogen were determined in 28 clinically normal horses, including 13 adult geldings, five non-pregnant mares, five pregnant mares and five yearlings (two fillies, three geldings). Plasminogen was quantitated by a chromogenic assay based on activation of plasmin by excess urokinase. The overall mean plasma plasminogen for these horses was 2.94 +/- 0.54 CTA units (casein units, as defined by the Committee on Thrombolytic Agents) per ml. There were no significant differences in mean plasma plasminogen values among adult geldings, non-pregnant mares, pregnant mares or yearling horses (P greater than 0.05).
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PMID:Plasma plasminogen concentrations in clinically normal horses: the effect of age, sex and pregnancy. 270 28

Metastatic spread of malignant tumor appears to correlate with activation of the fibrolytic system. The role of fibrinolysis in growth and metastasis was examined in Lewis lung carcinoma of mice. The inhibition of fibrinolysis or proteases decreased the primary tumor growth and pulmonary metastasis, whereas the activation of fibrinolysis or proteases increased the number of metastatic foci in the lung. Electronmicroscopically, thrombus formation in the primary site prevented tumor invasion and metastasis formation. Plasminogen activator (PA) content of excised tumors was determined by SDS-PAGE, and major PA was found to be urokinase (UK) type. Immunohistochemical study with specific antisera was done. When tumor cells possessed a high level of UK, laminin and type IV collagen, components of the basement membrane, disappeared from tumor tissues. These findings suggest that PA through protease cascade plays a role in tumor invasion and metastasis. Clinically, patients with advanced cancer are usually in a hypercoagulable state with elevated fibrinogen, and fibrin deposition around tumor mass is a serious problem in cancer chemotherapy. UK infusion prior to 5-fluorouracil increased tissue concentration of antitumor agent. However, development of consumption coagulopathy characterized by progression from hypercoagulable state to disseminated intravascular coagulation has also been found in several cases.
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PMID:[Tumor metastasis and the fibrinolytic system]. 273 23


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