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)

In order to investigate the binding of pro-urokinase (pro-UK) in urine to fibrin/Celite, the property which led to its discovery, the effect of fibrin on the plasminogen activator activity of urine was studied. The plasminogen activator activity in urine was found to be consistently about 2-fold higher when measured by fibrin plate assay than by amidolytic substrate (S-2444), when normalized against the UK reference standard. When the amidolytic activity measurement was preceded by incubation of urine with soluble fibrin, a 2-fold increase in amidolytic activity was also found. Fibrin similarly increased plasmin generation in urine enriched with Glu- or Lys-plasminogen as determined by synthetic substrate S-2251. The observed promoting effect was common to several forms of soluble fibrin and was dose dependent, whereas fibrinogen had little effect. The promoting effect of fibrin was not expressed in the presence of pro-UK or two-chain UK (TC-UK) in buffer and therefore was attributed to another constituent of urine. Since the activity was inhibited by antibodies to UK but not to t-PA, it was called fibrin activatable UK (FA-UK). Gel filtration (Sephacryl-200) of urine revealed FA-UK activity in fractions eluting at a molecular weight of approximately 100K. A 100 K band of activity was also consistently seen when concentrated urine was subjected to zymography. Treatment of concentrated urine with hydroxylamine (1 M) eradicated both these activities and was associated with an increase in baseline amidolytic activity in the urine sample indicative of the release of UK from an inhibitor complex. Moreover, passage of urine over insolubilized monoclonal antibody against UK-inhibitor (PAI-3) complexes resulted in loss of FA-UK activity and of the 100 K band on the zymogram suggesting that the complex responsible for FA-UK was related to a PAI-3 complex. Since the FA-UK activity appeared to bind to fibrin/Celite, attempts were made to investigate complexation with pro-UK. Unfortunately, due to the instability of pro-UK in urine, no reliable data were obtained. It was concluded that PAI-3 may serve as a fibrin-interacting co-factor of UK, and therefore may play a role in fibrinolysis.
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PMID:Fibrin activatable urokinase (FA-UK): a latent form of UK found in urine related to a complex with an inhibitor/fibrin-interacting cofactor. 305 14

Seminiferous peritubular cells have previously been shown to secrete a protein termed P-Mod-S which modulates the functions of Sertoli cells. The present study provides an initial characterization of P-Mod-S and examines the actions of P-Mod-S on Sertoli cells. Gel filtration chromatography demonstrates that P-Mod-S has an apparent molecular weight of 70 000 that could not be dissociated to a lower molecular weight form. A 40- to 90-fold purification of P-Mod-S was obtained with a predicted half maximal effective concentration for Sertoli cells of less than 10(-9) M. Through an analysis of the actions of P-Mod-S on Sertoli cells it is demonstrated that P-Mod-S stimulates the Sertoli cell to a greater extent than any single hormone or vitamin known to influence the cell. P-Mod-S maximally stimulates testicular transferrin and androgen-binding protein production by Sertoli cells, but does not stimulate levels of plasminogen activator activity. P-Mod-S also appears to induce the synthesis of several proteins that are not detected in control non-treated Sertoli cell cultures. One such protein whose synthesis was stimulated by P-Mod-S treatment of Sertoli cells was a component having a molecular mass of 20 kDa. This 20 kDa Sertoli cell-secreted protein was specifically immunoprecipitated with an antibody against an epididymal lactalbumin-like protein. This implies that P-Mod-S can induce Sertoli cells to synthesize and secrete a lactalbumin-like protein. P-Mod-S was found not to contain mitogenic activity. Data presented indicate that testicular peritubular cells synthesize and secrete a 70 kDa non mitogenic paracrine factor termed P-Mod-S which has a dramatic influence on Sertoli cell functions. Results are discussed with respect to modulation of epithelial (Sertoli) cell functions by components produced by mesenchymal (peritubular) cells.
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PMID:Identification of a non-mitogenic paracrine factor involved in mesenchymal-epithelial cell interactions between testicular peritubular cells and Sertoli cells. 308 88

The purpose of this study was to determine whether human polymorphonuclear neutrophils (PMN), which share a common cell lineage with macrophages, could produce factors such as IL 1. Other properties which these two cell types share are their phagocytic nature and the common receptor and antigens on their cell surfaces. IL 1, in many of its physical, biochemical, and functional characteristics, is found to resemble endogenous pyrogen (EP). PMN have been cited as a possible cell source of EP, but there have also been reports in which the capacity of PMN to produce EP has been questioned. This study shows that normal human PMN can be stimulated by particulate agents such as zymosan and soluble agents such as phorbol myristic acetate to produce a factor(s) which induces proliferation of mouse thymocytes, i.e., PMN IL 1. This PMN IL 1 was released from PMN in a dose- and time-dependent fashion. PMN IL 1 was nondialyzable, was heat-labile, and was inactivated at pH below 5 and above 8. PMN IL 1 stimulated the proliferation of normal human synovial fibroblasts and caused release of a neutral protease (plasminogen activator) from synovial cells. The synovial and thymocyte-proliferating capacity of PMN IL 1 was not affected by the protease inhibitor aprotinin or by soybean trypsin inhibitor. Gel filtration studies estimate the m.w. of PMN IL 1 to be approximately 13,000 to 17,000.
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PMID:Interleukin 1 production by human polymorphonuclear neutrophils. 308 39

The inhibition of one-chain and two-chain molecular forms of human tissue-type plasminogen activator (t-PA) by the fast-acting inhibitor of plasminogen activator (PA-inhibitor) present in plasma was studied in vitro and in vivo in rabbits. In vitro, both one-chain and two-chain forms of t-PA were neutralized very rapidly in rabbit plasma with high levels of PA-inhibitor. The rate constant of the interaction between two-chain t-PA and PA-inhibitor was estimated to be 3.10(7) L/mol/sec. The presence of CNBr-digested fibrinogen, which mimics the effect of fibrin on the activation of plasminogen by t-PA, did not influence the rate constant. Moreover, PA-inhibitor-rich plasma inhibited in a very similar way in vitro thrombolysis by one-chain or two-chain t-PA incorporated into the clot. Injection of one-chain or two-chain t-PA into rabbits with increased levels of PA-inhibitor, induced by endotoxin, resulted in very rapid inhibition of t-PA activity. Within 30 seconds after injection, no residual free t-PA could be demonstrated. Gel filtration analysis showed that the disappearance of t-PA activity was associated with the generation of t-PA-PA-inhibitor complex with an apparent Mr of 100,000. This enzyme-inhibitor complex, like free t-PA, was cleared from the circulation with a half-life of approximately 2 minutes, mainly via the liver. It is concluded that PA-inhibitor neutralizes one-chain and two-chain molecular forms of t-PA in plasma at very similar rates, both in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo. 308 73

We have previously described a factor(s) produced by 8387 fibrosarcoma cells, which can affect plasminogen activator (PA) activity of cultured cells. Since then, transforming growth factor-beta (TGF beta) has been established as a major growth factor/growth inhibitor that regulates both the expression and activity of PAs and their endothelial-type inhibitor (PAI-1). The present study was undertaken to characterize the 8387 fibrosarcoma cell-derived factor(s) and to investigate its relationships to TGF beta by analysis of modulation of PA activity and cell growth. The fibrosarcoma cell-derived proteins were partially purified from serum-free conditioned culture medium using Bio-Gel P-10 chromatography. Two separate fractions with apparent molecular weights of 16,000 and 12,000 contained activities that both decreased the secretion of PA activity by human lung fibroblasts and inhibited the soft agar growth of A549 lung adenocarcinoma cells. Both factors affected similarly the production of urokinase-type PA and PAI-1 in various cell lines and enhanced anchorage-independent growth of murine AKR-2B fibroblasts. The effects of these factors thus resembled those of TGF beta. The immunological relationships between the Mr 16,000 and Mr 12,000 factors and TGF beta were therefore studied using neutralizing anti-TGF beta antibodies. The TGF beta antibodies efficiently inhibited the effects of the Mr 16,000 factor but not those of the Mr 12,000 factor in cell culture assays. The results suggest that 8387 fibrosarcoma cells produce two major growth inhibitors, one of which is closely related to TGF beta.
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PMID:Modulation of extracellular proteolytic activity and anchorage-independent growth of cultured cells by sarcoma cell-derived factors: relationships to transforming growth factor-beta. 325 33

Poly(A)+-RNA from human kidney and human embryonal lung fibroblasts fractionated by sucrose gradient centrifugation was translated in Xenopus oocytes. Assay for plasminogen-dependent fibrinolytic activity detected synthesis of secreted plasminogen activator and revealed the active fraction of poly(A)+-RNA with a sedimentation coefficient of approximately 23S. Translation products of the active fraction were immunoadsorbed by antiurokinase monoclonal antibodies immobilized on sepharose. Gel electrophoretic analysis of the protein products showed that the 23S fraction of poly(A)+-RNA from human kidney contains mRNA for single-chain urokinase-type plasminogen activator with apparent molecular weight of approximately 50 kDa.
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PMID:[mRNA for the plasminogen activator of the urokinase type: translation in oocytes of Xenopus laevis]. 339 55

24 established melanoma cell cultures were screened for their secretion of plasminogen activators and plasminogen activator inhibitors into the culture medium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by conventional and reverse fibrin autography. Among the cell lines investigated, 22 cell lines predominantly secreting tissue type plasminogen activator (t-PA) and four cell lines additionally secreting urokinase were found. The conditioned media of two cell lines (KRFM and MJZJ) were found to contain plasminogen activator inhibitor (PAI) activity at a Mr position of approximately 50,000. The PAI of one of the two melanoma cell (MJZJ)-conditioned media found to contain PAI activity was purified to apparent homogeneity employing concanavalin A-Sepharose chromatography, gel filtration on Sephadex G-150, chromatography on Affi-Gel blue, and affinity chromatography on a Sepharose 4B immobilized monoclonal anti-t-PA IgG column. The purified melanoma PAI was found to be a single chain protein, acid stable, immunologically related to the endothelial derived PAI. In contrast to endothelial PAI, melanoma PAI presented itself in the conditioned media of the melanoma cells and in the purified preparation to an appreciable extent in its active form.
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PMID:Purification of an active plasminogen activator inhibitor immunologically related to the endothelial type plasminogen activator inhibitor from the conditioned media of a human melanoma cell line. 349 Apr 74

Neutrophil elastase digests plasminogen to yield a fragment, mini-plasminogen, which is activatable to a mini-plasmin capable of escaping the action of the primary plasmin inhibitor. Such a molecule may play a role in joint destruction, either directly or by activation of procollagenase to collagenase. Synovial fluid samples from 34 acute joint effusions were examined by lysine-Sepharose chromatography and fibrinolytic assay of the fall-through (non-lysine-binding) fractions in presence of urokinase. Fragments similar to mini-plasminogen were found in 20 of 23 inflammatory effusions (cell count greater than 0.5 X 10(3)/microliter) and in none of 11 non-inflammatory (traumatic and osteoarthritic) effusions (cell count less than 0.5 X 10(3)/microliter) (p less than 0.001). Analysis of four inflammatory fluids by gel filtration on Bio-Gel P 100 and enzyme-linked immunoassay for plasminogen antigen revealed plasminogen fragments with molecular weight similar to mini-plasminogen (34,000 daltons) in three, and larger plasminogen fragments (or complexes of mini-plasminogen with other synovial fluid macromolecules) in all four. Fibrinolytic activity was demonstrable in fractions containing plasminogen fragments after treatment with tissue type plasminogen activator. In contrast with non-inflammatory effusions, inflammatory joint fluids contain plasminogen fragments with the properties of mini-plasminogen, suggesting their possible role in inflammatory joint destruction.
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PMID:Mini-plasminogen-like fragments of plasminogen in synovial fluid in acute inflammatory arthritis. 363 68

In separate experiments, antibodies to plasminogen, factor X and protein C were applied to microtitre trays as commonly used in enzyme-linked immunoassays. After incubation with dilute normal human plasma as a source of the corresponding proenzyme antigen, the wells were exposed to dilutions of various snake venoms. After thorough washing, the microtitre tray wells were tested overnight with chromogenic tripeptide substrates known to be relatively specific for the activated forms of the above factors, i.e., plasmin, factor Xa and activated protein C. The immunochromometric assay described detected two new activators of protein C in Agkistrodon piscivorus and Agkistrodon contortrix venoms and a new factor X activator in Agkistrodon rhodostoma venom. Gel filtration of the latter venom indicated that the factor X activator eluted with high molecular weight, was clearly distinct from the peak fibrinogen clotting activity (Ancrod) and appeared to have no procoagulant activity. Although several Bothrops venoms appeared to contain plasminogen activator by this technique, the observed strong chromogenic activity was observed in microtitre wells independently of plasminogen and represented nonspecific amidase activity.
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PMID:Detection of specific proenzyme activators in snake venoms by a new immunoabsorbant-chromogenic substrate method. 384 Oct 12

Endotoxin producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 +/- 0.7 to 41 +/- 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator compatible with the formation of an enzyme-inhibitor complex with an apparent molecular weight of 100,000. Injection of human t-PA (1,500 IU/kg body wt) in endotoxin treated animals resulted in very fast inhibition of t-PA and formation of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was about 7 min as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in enhanced rate of accumulation of PA-inhibitor activity in the culture medium (two- to sevenfold increase). In five patients with septicemia, markedly increased levels of PA-inhibitor (14.3 +/- 15.5 U/ml) as compared with control subjects (1.3 +/- 0.7 U/ml) were observed in plasma. A very strong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. These data suggest that the appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.
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PMID:Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. 392 Feb 45


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