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)

The capacity of human monocytoid cell lines and peripheral blood monocytes to modulate their expression of plasminogen receptors has been assessed. After PMA stimulation, THP-1 or U937 monocytoid cells were separated into adherent and nonadherent populations. Plasminogen bound to adherent cells with similar capacity and affinity as to nonstimulated cells. In contrast, the nonadherent cells bound plasminogen with 5-17-fold higher capacity (without a change in affinity). This increase was selective as urokinase bound with similar affinity and capacity to the adherent and nonadherent populations. Upregulation of plasminogen receptors on the nonadherent monocytoid cells was rapid, detectable within 30 min, and reversible, adhesion of the nonadherent cells resulted in a sixfold decrease in plasminogen binding within 90 min. The increase in plasminogen binding to the nonadherent cells was associated with a marked increase in their capacity to generate plasmin activity from cell-bound plasminogen. PMA stimulation of human peripheral blood monocytes increased their expression of plasminogen receptors by two- to fourfold. This increase was observed in both adherent and nonadherent monocytes. Freshly isolated monocytes maximally bound 5.0 x 10(5) plasminogen molecules per cell, whereas monocytes cultured for 18 h or more maximally bound 1.7 x 10(7) molecules per cell, a 30-fold difference in receptor number. These results indicate that both monocytes and monocytoid cell lines can rapidly and markedly regulate their expression of plasminogen binding sites. As enhanced plasminogen binding is correlated with an increased capacity to generate plasmin, an enzyme with broad substrate recognition, modulation of plasminogen receptors may have profound functional consequences.
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PMID:Regulation of plasminogen receptor expression on human monocytes and monocytoid cell lines. 217 Apr 26

Plasminogen activator (PA) activities were measured in extracts of ventral and dorsolateral prostate lobes in Fischer 344 (F344) rats of different ages. Ventral prostates of 30-month-old animals demonstrated widespread epithelial atrophy, some foci of inflammation, intraglandular atypical hyperplasia and/or adenocarcinoma, and a marked increase in PA activities compared with younger animals. Both low- and high-molecular-weight forms of activator were found in zymograms and both forms of activator showed an increase at 30 months. However, the PA activity of the aged rats showed a greater resistance to amiloride inhibition, suggesting a greater relative increase in the tissue-type activator activity than that of urokinase. These changes were not observed in the dorsolateral prostate. The lobe-specific changes in activator activity appear related to dysplasia/neoplasia and not aging.
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PMID:Plasminogen activator activities in the ventral and dorsolateral prostatic lobes of aging Fischer 344 rats. 218 19

Plasminogen activators (PAs) are specific proteolytic enzymes which convert the inactive proenzyme plasminogen to plasmin. The plasmin formed is a potent and nonspecific protease which cleaves blood fibrin clots and several other extracellular proteins. In addition to their primary role in the initiation of fibrinolysis, PAs are implicated in a variety of basic biological processes, such as, degradation of the extracellular matrix, tumor invasiveness, tissue remodelling, and cellular differentiation. This review describes recent observations on the biochemical and biophysical characteristics of the different components of the plasminogen activation system. This complex system includes: the proenzymes of tissue type PA (tPA) and urokinase type PA (uPA); the active enzymes tPA, uPA and plasmin; the substrate plasminogen; several natural inhibitors of PA and plasmin activity; and the cellular receptors that bind the proenzymes, enzymes, and inhibitor-enzyme complexes. Through the coordinated interactions of these components, the location, timing, and extent of potent proteolytic activity is controlled. Recent findings on the structure, properties, biological functions, and regulation of the different components of the plasminogen activation cascade are reviewed. Current methods for assay of the amount and activity of the enzymes, inhibitors, and receptors are described. Observations implying specific functions of the system in health and disease, and its potential utilization for diagnosis are examined. Specifically, the potential application of PAs as laboratory markers of neoplasia, as diagnostic tools in diseases of the blood clotting system, their use for monitoring of thrombolytic therapy, and their possible relevance in certain disease states are described.
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PMID:Biochemical and biological aspects of the plasminogen activation system. 219 30

Plasminogen activators (PAs), were estimated qualitatively and quantitatively in two different clonal murine skeletal muscle cell lines. Both cell lines produced the two major types of PAs found in mammalian cells, urokinase-type (uPA) and tissue type (tPA). These two lines are models for the study of myogenesis in vitro, but differ in several growth and differentiation characteristics. Because of their possible involvement in these characteristics we assayed the expression of PAs in both cell systems during development in culture. Utilizing fibrin zymography two isoforms of tPA were detected. One co-migrated with human tPA at 75 kd and another may represent a tPA:inhibitor complex at 105 Kd. Several isoenzymes of uPA were detected and these changed depending on whether cell homogenates or conditioned medium was analyzed and whether myogenic cells were at single-cell myoblast or multi-nucleated myotube stage. Species-specific antisera to mouse uPA identified 4 uPA bands in muscle cell medium and 5 in cell layers. Antigenic uPA bands also varied depending on stage of myogenesis. Quantitative amidolytic studies using chromogenic substrates showed that maximal PA activity, both uPA and tPA, occurred at the time of myoblast fusion. Furthermore, uPA activity in membranes increased during myogenesis, while both uPA and tPA in medium decreased after fusion. These studies indicate that muscle PA expression is developmentally regulated and may correlate with growth and differentiation in skeletal muscle.
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PMID:Plasminogen activators and their inhibitors in the neuromuscular system: I. Developmental regulation of plasminogen activator isoforms during in vitro myogenesis in two cell lines. 219 66

We have investigated whether lymphatic endothelial cells in culture produce plasminogen activators (PAs) and their inhibitors (PAIs) and if these activities can be modulated by the inflammatory cytokine Tumor Necrosis Factor alpha (TNF-alpha). Examination by reverse fibrin autography of the conditioned medium from these cells revealed a PAI of Mr 50 kDa. Also evident by fibrin autography were two species of PAs, of Mr 110 kDa and Mr 60 kDa. The 110 kDa protein co-migrated with the PA-PAI complexes and the 60 kDa protein co-migrated with tissue Plasminogen Activator (tPA). Functional and immunological assays indicated the human TNF-alpha increased the type 1 plasminogen activator inhibitor (PAI-1) in a time dependent manner. Treatment of the cells with recombinant human TNF-alpha for 24 hours resulted in a 3 to 7 fold increase in the amount of PAI released into the conditioned media. Immunoblot analysis identified the PAI in the TNF-alpha treated cell conditioned media, as PAI-1. Deposition of PAI-1 in the extracellular matrix then became apparent. TNF-alpha increased 4 fold the amount of tPA-PAI-1 complexes (Mr 110 kDa) detected in the conditioned media. Free tPA (Mr 60 kDa) decreased to 1/5 of control. Net fibrinolytic activity, as determined by a chromogenic substrate assay, decreased after TNF-alpha treatment. No urokinase type Plasminogen Activator (uPA) activity was detected in control or treated cells. This fibrinolytic activity may be important in maintaining free fluid movement in the interstitium and lymphatic vessels and in inflammatory states this potential may be decreased by the increase in PAI-1.
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PMID:Production of plasminogen activator and plasminogen activator inhibitor by bovine lymphatic endothelial cells: modulation by TNF-alpha. 223 28

Plasminogen activator activity in normal human tears was found to be 0.03 +/- 0.02 IU/ml with casein plate, and 0.06 +/- 0.04 IU/ml with a spectrophotometric method. Elevated levels of plasminogen activator activity (range 0.11-2.05 IU/ml) were detected in the tear fluid of patients suffering from various corneal and conjunctival diseases including corneal ulcers, superficial keratitis, persistent epithelial defects, recurrent erosions, bullous keratopathy, contact lens associated erosions, alkali burns of the cornea, Mooren's ulcer, conjunctival pemphigoid, acute keratoconus, and corneal melanoma. Plasminogen activator activity, determined in the absence of fibrin in tear samples collected by capillary tubes at low flow rates, is considered to be the result of the presence of urokinase-type plasminogen activator (uPA) deriving from the epithelial cells of the cornea and the conjunctiva. It is suggested that an increase in the level of uPA in tears plays an important role not only in ulceration (the formation and repair of epithelial and stromal defects), but also in the development and healing of a number of other inflammatory processes, infections, immunological processes, chemical burns, contact lens associated lesions; in the invasion of microorganisms and leukocytes, in edema formation, in neovascularization, and in the invasive growth of tumors in the cornea and the conjunctiva.
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PMID:Determination of plasminogen activator activities in normal and pathological human tears. The significance of tear plasminogen activators in the inflammatory and traumatic lesions of the cornea and the conjunctiva. 227 42

We examined fibrinolytic substances in homogenate of leukemic cells, normal granulocyte or mononuclear cells fraction. Plasminogen activators (PA) were significantly low in normal cells, but they were slightly increased in lymphoblastic leukemia cells and markedly increased in myeloblastic leukemia cells. In almost leukemic cells homogenate, the antigen ratio of tissue type PA (t-PA)/urokinase type PA (u-PA) was about 2.0. In especially AMMoL and AMoL, PA activity had discrepancy between euglobulin lysis time and amidolytic assay using chromogenic substrate. As PA inhibitor (PAI)-II was markedly increased in them. PAI might effect the PA assay. PA activity of leukemic cells homogenate was similar to that without t-PA stimulator and leukemic cells homogenate significantly stimulated t-PA. As both PA activity and antigen were statistically increased in leukemic cells homogenate of patient with disseminated intravascular coagulation (DIC), PA and PA stimulator in leukemic cell might play an important role in hypofibrinogenemia or DIC.
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PMID:[Plasminogen activator in leukemic cell homogenate]. 228 63

Abundant deposition of bronchoalveolar fibrin and fibronectin occurs during the exudative phase of the adult respiratory distress syndrome (ARDS), promoting hyaline-membrane formation and subsequent alveolar fibrosis. To explore the mechanisms that account for the persistence of bronchoalveolar fibrin and fibronectin, we compared the activity of urokinase, which is necessary for plasminogen activation and fibrin degradation, in cell-free bronchoalveolar-lavage fluid from 8 patients with ARDS, 9 patients with acute pulmonary diseases other than ARDS, and 10 normal subjects. The mean level of urokinase activity in the lavage fluid from the patients with ARDS was 0.003 IU per milliliter of fluid (range, 0 to 0.008), which was significantly lower (P = 0.001) than the level in the fluid from either the patients with pulmonary diseases other than ARDS (0.118 IU per milliliter [range, 0.032 to 0.295]) or the normal subjects (0.129 IU per milliliter [range, 0.045 to 0.198]). The lavage fluid from all the patients with ARDS also had antiplasmin activity, which would promote the persistence of fibrin. A true decrease in urokinase activity was confirmed by the failure of the lavage fluid from the patients with ARDS to convert [125I]plasminogen to plasmin. Despite the low urokinase activity, immunochemical assays revealed normal levels of urokinase antigen in the fluid from the patients with ARDS, suggesting the presence of urokinase inhibitors. Inhibitors were demonstrated directly by a fibrin gel-underlay assay that detects complexes of urokinase with inhibitors. Plasminogen-activator inhibitor type 1 was the principal inhibitor identified. We conclude that increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS.
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PMID:Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. 231 27

Plasminogen activator activity was determined in stimulated normal rabbit tears, and was identified as being due to urokinase using specific antibodies. The activator activity is about 100-fold higher in rabbit tears than in human tears. The molecular weight of the activator was determined by fibrin zymography to be 40-50 kDa. However, a multiband pattern of urokinase-type antigen ranging in molecular weight from 60-70 kDa to 200 kDa was detected by immunoblotting. The 60-70 kDa protein was resistant to reduction. The antigen concentration is more than 100-fold higher than the concentration expected from the activity measurement, indicating that most of the urokinase in rabbit tears is in inactive form, such as in inhibitor or receptor complexes.
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PMID:Urokinase-type plasminogen activator in rabbit tears. Comparison with human tears. 237 78

The relationship of plasminogen activator (PA) production to cell stage, cell number and changes in overall diameter and zona pellucida thickness for bovine embryos developing in vitro was determined. Late morulae to blastocysts (n = 80) were collected nonsurgically from naturally mated, estrous-synchronized, superovulated crossbred beef cows. Embryos were cultured, one embryo per 25-microliters microdrop, for 6 d. At 24-h intervals, embryos were evaluated for stage of development and transferred to fresh microdrops; media were recovered for PA analysis. In addition, embryo diameter and zona pellucida thickness were measured with an ocular micrometer. Plasminogen activator production was determined using a caseinolytic assay with urokinase as the standard. Changes in diameter, zona pellucida thickness and PA production per 24-h interval for each embryo were plotted, and the graphs were cut out and weighed. Sixty-one embryos (76%) completed the hatching process. Total PA production was correlated positively (P less than .005) to embryonic size (r = .40), developmental stage (r = .35) and cell number (r = .35) and negatively, but weakly, correlated to zona pellucida thickness (r = -.13; P = .267). Hatched embryos produced more total PA than embryos that did not hatch (.140 +/- .011 vs .070 +/- .019 g; P less than .01). These results suggest that as embryonic size and cell number increase and development progresses, bovine embryos liberate more PA.
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PMID:Relationship between plasminogen activator production and bovine embryo development in vitro. 238 91


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