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)

Plasminogen, the inactive precursor of plasmin, a general trypsin-like proteinase, is present at high concentration in blood and in body fluids. Most cells can recruit this proteolytic potential by secreting plasminogen activator (PA) to generate localized proteolysis in the surrounding microenvironment. PA and plasmin are serine enzymes whose pH optima match extracellular pH; further, in view of the large amount of circulating proenzyme and the broad substrate range of plasmin, the possibility that this proteolytic system can initiate a variety of proteolytic reactions or sequences should be kept in mind. PA production is precisely regulated by hormones, temporal programming, or both; and enzyme synthesis is correlated with some physiological and pathological processes requiring proteolysis. Thus PA production is coordinately regulated with ovulation, trophoblast implantation, spermatogenesis, polypeptide hormone synthesis, and some developmental phenomena; and with inflammation, tumour promotion, and neoplasia. Tissue remodelling and cell migration are common to many of these processes. Macrophage (monocyte) and polymorphonuclear leucocyte PA production is modulated by many biologically active substances. Enzyme synthesis is induced and stimulated by stimuli that recruit these cells to sites of inflammation, and it is repressed by anti-inflammatory agents, notably by glucocorticoids.
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PMID:Neutral proteinases of leucocytes and the inflammatory process. 39 97

A fibrin slide test was utilized to study cutaneous vascular plasminogen activator activity in normal rabbit, rat, monkey, and human skin and in rabbit skin following development of the local Shwartzman reaction and after substituting epsilon-aminocaproic acid for the preparatory injection of endotoxin in the local Shwartzman reaction. Cutaneous vascular plasminogen activator activity was also studied in rats after attempted induction of the local Shwartzman reaction following inhibition of fibrinolysis with epsilon-aminocaproic acid and/or pregnancy. Plasminogen activator activity was detected in vessels of normal rat, monkey, and human skin but was absent in skin from normal rabbits and rabbits with the local Shwartzman reaction. Intradermal injection of epsilon-aminocaproic acid failed to prepare for the local Shwartzman reaction. In the rat, which has greater cutaneous vascular plasminogen activator activity than the rabbit, inhibition of vascular activator with epsilon-aminocaproic acid and/or pregnancy failed to prepare for the local Shwartzman reaction. These studies indicate that although the markedly diminished level of cutaneous vascular plasminogen activator in the rabbit may be important in the pathogenesis of the local Shwatzman reaction, factors other than inhibition of fibrinolysis are also necessary for preparation of the reaction.
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PMID:Cutaneous vascular fibrinolytic activity in the local Shwartzman reaction. 40 99

We have analyzed the plasminogen activator (PA) content of normal rodent mammary glands at different stages of the mammary life cycle and after exposing the animals to various hormones; we have also assessed the PA response of mammary explants to a variety of hormonal environments. Similar studies were performed on a limited number of primary mammary tumors. Plasminogen activator production was clearly correlated with mammary involution. A large but transient increase in enzyme content followed the initiation of involution in all glands, and the enzyme was produced by mammary cells, not by macrophages or granulocytes. Oxytocin, prolactin and hydrocortisone, which slowed or blocked involution, produced parallel effects on gland regression and PA synthesis. PA synthesis by explants in organ culture was induced by hormonal environments that fostered involution and repressed by those that promoted lactation. Mammary tumors produced much more PA than normal tissue both in vivo and in vitro, and distinct differences were found in the response of enzyme synthesis to hormones. The results reinforce the association of PA with tissue remodeling; show that the enzyme can be used as an indicator of cellular response to a wide range of hormones in both normal and malignant tissue; and suggest that observations of this type in organ culture may be of some value in predicting physiological responses in vivo.
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PMID:Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. 45 56

Normal human plasma contains acid-stable as well as labile plasminogen activators. The activity of activators in plasma euglobulins was inhibited by EACA in an uniform pattern, similar to that obtained with the major activators in human uterine tissue or with the purified porcine tissue activator, but different from the patterns obtained with plasmin or with urokinase. Gel filtration at high ionic strength separated activators corresponding to particle sizes of 60,000 dalton and about 10,000 dalton, corresponding to two activators similarly obtained from human tissue. The 60,000 dalton activator was precipitated in the euglobulin fraction. Its concentration increased in plasma after exercise. The 10,000 dalton activator was found mainly in the supernatant. Gel filtration in 0.15 M solutions yielded activators in fractions of molecular sizes of 100-140,000 dalton and 200,000 dalton or larger. The activity of normal and exercise euglobulins was inhibited by antiserum to a plasminogen activator prepared from porcine tissue, but it was not inhibited by antiserum to urokinase. Plasminogen activators in human plasma euglobulins resembled immunochemically the activators in human uterine tissue.
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PMID:Separation of plasminogen activators from human plasma and a comparison with activators from human uterine tissue and urine. 48 46

Plasminogen activator activity was detected in human gynecologic specimens using a synthetic fluorogenic peptide substrate assay and confirmed by an 125I-labeled fibrin plate assay. Epithelial cells in these samples contain enzymatic activity that biochemically resembles both the well-characterized plasminogen activator, urokinase, and the less-specific plasminogen activator, trypsin. Inhibition of the cervical cell activity by diisopropylfluorophosphate and p-nitrophenyl-p'-guanidinobenzoate demonstrates that, like urokinase and trypsin, this plasminogen activator is also a serine protease. Polyacrylamide gel electrophoresis of plasminogen that had been incubated with cervical cells indicated the same mechanism of plasminogen activation as exhibited by urokinase. We attempted to correlate plasminogen activator activity of each sample with cytomorphologic diagnosis. Three of the four dysplastic samples analyzed showed higher plasminogen activator activity than did the normal samples.
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PMID:Characterization of plasminogen activator in human cervical cells. 65 74

Plasminogen activator secretion by 39 primary or early-passage cultures of malignant human neoplasms has been compared with that of 16 similar cultures of benign neoplasms and 39 cultures of normal or reactive tissue. While normal cells of mesenchymal or neural origin secreted considerably less plasminogen activator than did cells from frankly malignant tissues, elevated levels of enzyme secretion were also encountered in cultures of benign neoplastic or reactive cells. In the case of epithelial tissue, no consistent relationship between plasminogen activator secretion and neoplasia could be documented. Our failure to observe, for any particular cell type, a reproducible correlation between malignancy and plasminogen activator secretion may be attributable to the artificial conditions of in vitro culture, where normal in vivo regulatory mechanisms do not obtain.
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PMID:Secretion of plasminogen activator by normal, reactive and neoplastic human tissues cultured in vitro. 70 Aug 94

Plasminogen activator contains equimolar proportions of streptokinase and human plasminogen, and as proactivator-streptokinase complex it has activator properties. In nine patients with recent venous thromboses of the upper or lower limbs plasminogen activator treatment achieved complete recanalisation in 14 of 27 veins occluded by thrombosis and partially in six. Clotting tests indicated that activator treatment can be better controlled than streptokinase treatment.
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PMID:[Activator treatment of acute venous thrombosis (author's transl)]. 71 Mar 20

Several molecular weight forms of plasminogen activator (PA) activity have been observed in serum-free conditioned media from human cells in culture. An antibody inhibition technique is described which combines inhibition of enzyme activity by anti-urokinase IgG with sodium dodecyl sulfate-gel electrophoresis to determine whether different molecular weight forms of human cell PA's are immunologically related to urokinase. Plasminogen activator forms with molecular weights of 85,000 to 95,000, 50,000 to 60,000, and 36,000 were inhibited by anti-urokinase IgG. In contrast, PA forms with molecular weights in the 73,000 range from three different types of human cells were not inhibited by comparable concentrations of the antibody. Human embryonic kidney cultures contain only anti-urokinase IgG-inhibitable PA forms, while melanoma-derived Malme-3M cultures contain only anti-urokinase IgG-resistant forms. Cultures of tumorigenic Detroit 562 cells and nontumorigenic IMR-90 cells contain a mixture of "antibody-sensitive" and "antibody-resistant" PA forms. The antibody-resistant 73,000-dalton PA form may be a precursor of the smaller antibody-sensitive, urokinase-related forms, or it may be the product of a second plasminogen activator gene which codes for a protein immunologically and structurally different from urokinase.
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PMID:Immunological characterization of multiple weight forms of human cell plasminogen activators. 76 81

Macrophages obtained from the peritoneal cavity of untreated mice do not ordinarily synthesize plasminogen activator. However, induction of enzyme synthesis and secretion occurs when such macrophages are cultured in presence of conditioned medium from Con A-stimulated spleen cells. Plasminogen activator production by macrophages from endotoxin or thioglycollate medium-injected mice, which spontaneously secrete substantial amounts of the enzyme, is also markedly increased in presence of such conditioned medium. These results suggest that macrophage plasminogen activatory production may be regulated in part by lymphocytes. They provide further evidence to link macrophage plasminogen activator with cell migration and inflammation, and also support the view that in macrophages, as in certain other cell types, synthesis and secretion of this enzyme are under hormonal control.
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PMID:Macrophage plasminogen activator: induction by products of activated lymphoid cells. 83 46

Lysozyme, alpha-amylase, neutral proteinase and plasminogen activator were most concentrated in the initial portion of the ejaculate that consists mostly of Cowper's gland and prostate gland fluids as well as spermatozoa. The concentration of the high molecular weight proteinase inhibitors, alpha1-antitrypsin and alpha1X-antichymotrypsin, was essentially unaltered throughout the ejaculate fractions, although their absolute amounts showed an increase towards the final fraction. By contrast, the total inhibitory activity towards pancreatic trypsin was highest both in concentration and amount in the last fraction, thus indicating that the seminal vesicles are its primary source. Plasminogen, prothrombin, Factor XIII, and the proteinase inhibitors antithrombin III, alpha2-macroglobulin, inter-alpha-trypsin inhibitor and C1S-inactivator could not be detected immunochemically in whole ejaculates, and indicates the dissimilarity between the coagulation/liquefaction processes of semen and blood.
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PMID:Components of human split ejaculates. II. Enzymes and proteinase inhibitors. 108 6


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