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)

Changes in plasminogen activator activity have been examined as a clonal line of mouse embryonal carcinoma cells aggregate and differentiate to form cystic embryoid bodies in vitro. Within the first 10 days of study, the pluripotent embryonal carcinoma cells aggregate; a layer of endodermal cells appears on the outside of the aggregate forming an embryoid body; a basement membrane forms between the outer layer of endodermal cells and the internal cells; a cyst forms within the embryoid body; and the internal cells assume a columnar appearance along the inner portion of the basement membrane. After the formation of the endodermal layer, there is a rise in intracellular plasminogen activator activity. This rise continues for up to 25 days in culture, providing that the three-dimensional integrity of the embryoid bodies is maintained by culturing them on bacterial petri dishes. Selective removal of the outer endodermal layer of cells reduces the plasminogen activatory activity of the resulting embryoid body cores. Intracellular and secreted plasminogen activator activity of simple embryoid bodies composed of only two cell types can be increased by culturing the embryoid bodies in dbcAMP, theophylline, or cholera toxin. These results suggest that the embryoid body endodermal cells are the source of a cAMP-inducible plasminogen activator activity.
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PMID:Teratocarcinoma differentiation: plasminogen activator activity associated with embryoid body formation. 18 37

Purified human PMNs secrete plasminogen activator. This secretion is stimulated by Con A and low concentrations of PMA, and is inhibited by low concentrations of glucocorticoids, and by cAMP, actinomycin D, and cycloheximide. In contrast, the release of granule-bound enzymes, such as elastase, is achieved only at higher concentrations of PMA, and is not affected by any of the inhibitors that block plasminogen activator production. These results show that the production of plasminogen activatory by PMNs is controlled by agents that affect inflammations, and that this control is not shared by other lytic enzymes known to be associated with these cells. This suggests a particular role for plasminogen activator in the response pattern of PMNs and also supports the concept, previously developed for macrophages, that the secretion of this enzyme is correlated with cell migration in vivo.
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PMID:Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other effectors. 20 Jun 99

A direct rate assay for plasminogen activator has been developed using a synthetic fluorogenic peptide substrate, 7-(N-Cbz-glycylglycylargininamido)-4-methylcoumarin trifluoroacetate. The assay correlates well with the standard 125I-labeled fibrin plate assay using highly purified urokinase, culture fluids from WI-38, Chinese hamster vary or HeLa cells, or Rous sarcoma virus-transformed chick fibroblasts as the source of plasminogen activator. The assay is sensitive, rapid, and linear throughout a wide range of enzyme concentrations. With this substrate it is possible to determine inhibitor profiles for the various plasminogen activators, independently of the interfering potential of plasmin. All of the enzymes tested are inhibited by leupeptin and antipain but not by the related aldehydes, elastatinal and chymostatin. The macromolecular inhibitors soybean trypsin inhibitor and trasylol have little or no effect on the plasminogen activators tested. This substrate should be useful for the study of the effect of various agents on functional changes in cells secreting this enzyme and also should allow kinetic measurements of potential inhibitors.
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PMID:Direct fluorescent assay of urokinase and plasminogen activators of normal and malignant cells: kinetics and inhibitor profiles. 20 31

Plasminogen activator is produced by hamster cells transformed by human herpesviruses. These cell lines have previously been shown to be oncogenic when injected s.c. into newborn syngeneic hamsters. Lysis of fibrin overlays by these cell lines was plasminogen dependent. Normal hamster embryo fibroblasts and a hamster cell line transformed by PARA-7 (an adenovirus-SV 40 hybrid) failed to produced lysis. In separate experiments fibrin overlay of lytically infected secondary rabbit kidney cells did not show induction of this activity during the normal course of productive infection. The human cell line TE-85 clone F-5, a clonal cell line from a human osteogenic sarcoma, failed to produce plasminogen activator, but two separate clones of these cells that were morphologically transformed after exposure to UV-inactivated herpes simplex virus type 2 produced rapid lysis of the fibrin overlay. Clonal variation was observed in herpes simplex virus types 1 and 2-transformed hamster lines and is under investigation. It is suggested that plasminogen activator detection may serve as a convenient assay system for transformation of normal cells by herpesviruses.
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PMID:Production of plasminogen activator by cells transformed by herpesviruses. 20 45

Clone B559 mouse melanoma cells are highly tumorigenic and produce plasminogen activator. Cells of clone C3471, a line obtained by continued growth of B559 cells in medium containing 5-bromodeoxyuridine (1 microgram/ml), have no plasminogen activator and are non-tumorigenic. When B559 cells are co-cultivated with C3471 cells, the ability of B559 cells to activate plasminogen is suppressed. Under these conditions cell fusion occurs. Lack of expression of plasminogen activators is not a consequence of cell fusion, inhibition of cell division or release of soluble inhibitors of either plasminogen activators or plasmin. No inhibitors of plasminogen activators could be demonstrated in association with sub cellular fractions of C3471 cells or with the C-type viral particles released from C3471 cells. Close contact between cells of the two lines is shown to be essential for suppression of plasminogen activation.
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PMID:Co-cultivation of tumorigenic mouse melanoma cells with cells of a non-tumorigenic subclone inhibits plasminogen activator expression by the melanoma cells. 20 66

A technique is described for detecting fibrinolytic activity of single cells in culture. This method was applied to the analysis of rat ovarian granulosa cells. Cells obtained from follicules shortly before ovulation show high levels of fibrinolytic activity. This activity is plasminogen-dependent, indicating that it is due to plasminogen activator. The appearance of this activity is correlated with ovulation by temporal and functional criteria, and can be demonstrated both in immature animals primed with hormones and in mature cycling animals. Granulosa cell cultures can be stimulated to release plasminogen activator by exposure in vitro either to luteinizing hormone or to dibutyryl cyclic AMP.
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PMID:Ovarian plasminogen activator: relationship to ovulation and hormonal regulation. 21 5

To explore the interaction of tumor promoters and sarcoma virus transformation with cellular regulatory mechanisms, we have studied induction of plasminogen activator synthesis by these agents in a background of changing cyclic nucleotide concentrations. We have confirmed the original report of Wigler and Weinstein (Nature, 259: 232, 1976) that phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces high levels of plasminogen activator production by chick embryo fibroblasts. Sarcoma virus transformation sensitizes the fibroblasts by lowering the threshold concentration for response to the action of PMA, and the effects of transformation and PMA on plasminogen activator synthesis are synergistic rather than additive. The plasminogen activators produced in the PMA-, virus-induced, or synergistically stimulated cultures are indistinguishable. Enzyme production in all three conditions is strongly but reversibly inhibited when cyclic nucleotide levels are raised by exposure to cyclic adenosine-3':5'-monophosphate or cholera toxin. A substantial fraction of the morphological effect that accompanies transformation is not affected by concentrations of cyclic nucleotides that suppress plasminogen activator production, and the two phenomena are therefore at least partially independent expressions of transformation in this system.
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PMID:Modulation of plasminogen activator synthesis in chick embryo fibroblasts by cyclic nucleotides and phorobol myristate acetate. 21 31

The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF). Following PMA treatment of serum-free RSVCEF cultures, PA induction is accompanied by distinct morphological changes, including enhanced cell clustering and the formation of dense cellular aggregates. These alterations in the morphology of the PMA-treated transformed cells are inhibited by several protease inhibitors, including leupeptin, NPGB, SBTI, benzamidine and DFP, the specific inhibitor of serine enzymes. A number of protease inhibitors are ineffective in preventing the PMA-induced morphological changes; these include inhibitors of trypsin, chymotrypsin, elastase, thrombin and, most importantly, plasmin. The use of a fluorescent substrate to assay PA directly demonstrated that the pattern of inhibiton of PA activity correlates exactly with the inhibition of morphological changes. The of 3H-DFP to label and characterize serine zymes in the culture fluid from PMA-treated cells further indicated that PA is the serine protease responsible for the morphological changes. Thus PA itself can catalytically alter cellular behavior in culture independent of plasminogen, until not its only known natural substrate.
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PMID:Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator. 22 74

A modified fibrin-agar overlay assay was used to measure the fibrinolytic activity in human cervical epithelial cells. The fibrinolytic activity results from a cell-associated serine protease that acts as a plasminogen activator. An enzymatic and morphologic comparison of individual normal and abnormal cells reveals that about 50% of the dysplastic and carcinoma in situ cells contain high levels of the activator. Forty percent of morphologically normal metaplastic cells also exhibit high activities of plasminogen. Forty percent of morphologically normal metaplastic cells also exhibit high activities of plasminogen activator. Most normal intermediate and superficial epithelial cells and all erythrocytes and leukocytes are inactive. The frequency of plasminogen activator-containing cells was somewhat higher in cytomorphologically abnormal samples than in normal samples.
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PMID:Plasminogen activator as a diagnostic marker for preneoplastic cells in human gynecologic specimens. 29 58

Mouse melanoma clones B559 and B78 are highly tumorigenic when injected into C57BL/6J mice. Tmor formation by these cells is suppressed when they are mixed with nonmalignant bromodeoxyuridine-grown clone C3471 before injection. C3471 cells suppress tumor formation only in immunocompetent hosts; mixtures of B559 and C3471 cells or C3471 cells alone form tumors in antithymocyte serum (ATS)-treated mice. Explants of C3471 tumors grown in ATS-treated mice form tumors in immunocompetent mice, most of which regress. Inability of C3471 or mixtures of C3471 with malignant cells to grow in normal mice, as contrasted with ability to grow in immunosuppressed mice, indicates that host response is involved. Both tumorigenic clones have high plasminogen activator activity, whereas nontumorigenic clone C3471 has none. Mixture of either tumorigenic clone with C3471 cells decreases plasminogen activator in vitro. C3471 tumor explants from ATS-treated mice initially express plasminogen activator, but lose the capacity to express this activity upon prolonged cultivation in vitro. Explants from B559 tumors retain plasminogen activator in long term culture. Close physical contact between C3471 and B559 cells appears essential both for inhibiton of plasminogen activator expression by B559 cells in vitro, and for tumor suppression in vivo. These findings suggest that production of plasminogen activators by tumor cells may play an important role in suppressing the host's immune response locally to an inoculum of syngeneic tumor cells.
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PMID:Malignant mouse melanoma cells do not form tumors when mixed with cells of a non-malignant subclone: relationships between plasminogen activator expression by the tumor cells and the host's immune response. 30 89


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