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)

For a period of 6 weeks, 76 healthy male volunteers consumed during their daily main meal the contents of one tin (approximately 135 g) of either fish (mackerel) paste or meat paste. Fibrinolytic parameters were determined in plasma samples obtained at the beginning and at the end of the experimental period. No changes were found in plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator (t-PA) antigen, and euglobulin t-PA activity. In the control group (n = 39), plasminogen activator inhibitor activity did not change. In the fish group (n = 37), however, total plasma PA inhibitor (PAI) activity increased by 45%, due to a 71% increase in PA inhibitor type-1. This increase could not be ascribed to a diet-induced acute phase-type reaction and could not be explained by changes in serum triglycerides or insulin.
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PMID:A moderate fish intake increases plasminogen activator inhibitor type-1 in human volunteers. 247 97

The regulation of urokinase secretion and receptor display in a well-differentiated colon carcinoma cell line, GEO, adapted to serum-free conditions was examined. In protein-free medium, the cell line secreted 0.8 +/- 0.1 ng/ml/10(6) cells of urokinase in a 3-day period as determined by an enzyme-linked immunosorbent assay. This value was elevated 4-fold when the cells were cultivated in the presence of epidermal growth factor (EGF) but not insulin or transferrin. Propagation of the cell line with any combination of these growth factors was not superior to EGF alone in inducing urokinase secretion. The presence of EGF raised the radioactive laminin-solubilizing activity of the conditioned medium. In the absence of the growth factor, spent medium supplemented with plasminogen solubilized 23,000 +/- 7,000 dpm/10(6) cells of the immobilized laminin. This value was increased to 95,000 +/- 10,000 dpm/10(6) cells when the cultures were grown with EGF. Northern analysis indicated that the elevated level of the plasminogen activator protein by EGF was a consequence of a more abundant urokinase transcript. The stimulation of urokinase secretion by EGF was accompanied by a reduction of radioactive urokinase binding to the cell line. The reduction in plasminogen activator binding was not further enhanced by insulin or transferrin. In addition, these latter growth factors, by themselves, were ineffective in altering the amount of plasminogen activator bound. The attenuation in 125I-labeled urokinase binding did not reflect occupation of the receptors with endogenous ligand as acid pretreatment was without effect on the binding profile. Scatchard analysis revealed that the altered urokinase binding by EGF reflected a decrease in receptor number from 14,000 +/- 1,500 to 8,000 +/- 1,500 sites per cell. The temporal relationship of urokinase secretion and receptor display was examined. Changes in either parameter required an EGF exposure period of 10 h or more. Further amplification of the EGF effects was seen with longer incubation times with the growth peptide. These opposite effects of EGF on urokinase secretion and receptor display may suggest a homeostatic control mechanism for keeping the plasminogen activator system in check. The ability of the cell line to express biological characteristics associated with a well-differentiated colon cell type may reflect its capacity to suppress a system which is usually associated with the transformed state.
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PMID:Determination of the effects of epidermal growth factor on urokinase secretion and urokinase receptor display in a well-differentiated human colon carcinoma cell line. 253 50

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 present study documents the effect of the planar, polar differentiation promoter N,N-dimethylformamide (DMF) on urokinase binding to colon carcinoma cells. Exposure of the colon carcinoma cell lines to the agent resulted in enhanced specific binding of radioactive urokinase to all cells tested. Insulin binding to the cells was, however, unaffected by DMF. A DMF exposure period of 45 h was required to observe maximum urokinase binding to two representative cell lines FET and RKO. Optimal stimulation of both cell lines occurred with 0.8% DMF. Scatchard analysis revealed the dissociation constants to be unchanged by the agent with the increased binding of radioactive plasminogen activator reflecting an up-regulation of binding sites. In this regard, the cell line RKO upon exposure to DMF, displayed approx. 700,000 receptors/cell, the highest value published, to date, for any cell line.
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PMID:Modulation of the urokinase receptor in human colon cell lines by N,N-dimethylformamide. 283 92

Using an in vitro system of pig Leydig cells (LC) and Sertoli cells (SC) we have demonstrated that: 1) LC contained specific receptors for both somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) and insulin, whereas SC contained only Sm-C/IGF-I receptors; 2) pretreatment of LC with insulin or Sm-C/IGF-I increased hCG receptor number and the cAMP and testosterone responses to this hormone. The enhanced steroidogenic capacity was related to an increased activity of several enzymes of the steroidogenic pathway. At physiological concentrations Sm-C/IGF-I was more potent than insulin, but the effects of the latter peptide at micromolar concentrations were similar to those produced by nanomolar concentrations of Sm-C/IGF-I. However, at maximal concentrations of both peptides, there was no additive effect; 3) the specificity of the effect of Sm-C/IGF-I was proven by the fact that all the effects induced by this peptide, but not by insulin, were blunted by an anti-Sm-C/IGF-I antibody; 4) pretreatment of SC with Sm-C/IGF-I at nM concentrations or with insulin (but only at microM concentrations) enhanced the stimulatory effect of FSH on cAMP production and the secretion of plasminogen activator; 5) in both LH and SC, Sm-C/IGF-I had small mitogenic effects but potentiated the mitogenic action of fibroblast growth factor (FGF). The effect of insulin was observed only at microM concentrations; 6) SC secreted a factor which had physico-chemical and biological properties similar to that of Sm-C/IGF-I. The secretion of this factor was stimulated by FGF and EGF.
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PMID:Differentiating effects of somatomedin-C/insulin-like growth factor I and insulin on Leydig and Sertoli cell functions. 285 90

Differentiated clonal cell lines were isolated from pluripotent P19 embryonal carcinoma (EC) cells treated as aggregates with retinoic acid. Two were characterized in detail. The lines differ in morphology, proliferation rate, the production of plasminogen activator, and in their mitogenic response to insulin but both produce extracellular matrix proteins and can be serially passaged over extended periods, in contrast to differentiated derivatives of many other EC lines. Further, both lines have receptors for and respond mitogenically to epidermal growth factor (EGF). Endogenous phosphorylation of several proteins, including the EGF receptor (150 kDa) and a 38-kDa protein, is induced by EGF in membranes isolated from these cells. Preincubation of membranes with EGF renders them able to catalyze phosphorylation of tyrosine residues in exogenously added peptide substrates. High voltage electrophoresis confirmed the tyrosine specificity of the phosphorylation on the 150- and 38-kDa bands. By contrast, similar experiments in undifferentiated cells showed that intact P19 EC neither bind nor respond to EGF mitogenically and EGF induces no changes in phosphorylation in isolated membranes.
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PMID:Clonal variants of differentiated P19 embryonal carcinoma cells exhibit epidermal growth factor receptor kinase activity. 298 69

Plasma membranes were isolated from the cultured Sertoli cells of 20-day-old rat testes by differential centrifugation and sucrose density fractionation. The distribution and purity of subcellular components was determined by marker enzyme analysis of gradient fractions. The plasma membrane fraction showed an enrichment in two plasma membrane marker enzymes, 5'-nucleotidase and ouabain-sensitive Na+/K+-ATPase-specific activities, of 9- and 23-fold, respectively. Forty-two percent and 52% of the total cellular 5'-nucleotidase and ouabain-sensitive Na+/K+-ATPase activities, respectively, were found in the membrane fraction. The protein yield of plasma membrane was approximately 6% of the total cellular protein. Two-dimensional polyacrylamide gel electrophoresis was used to compare [35S] methionine- and [3H] glucosamine-labeled membrane proteins. The incorporation of [35S] methionine and [3H] glucosamine was increased in several proteins when the cultured Sertoli cells were treated with follicle-stimulating hormone, insulin, retinol, and testosterone. Isolated Sertoli cell membranes contained a membrane-associated form of plasminogen activator. Analysis of this plasminogen activator demonstrated that the membrane-associated enzyme existed primarily as a single 38,000-40,000-Mr form.
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PMID:Isolation and characterization of Sertoli cell plasma membranes and associated plasminogen activator activity. 299 May 84

The cyclic secretion of plasminogen activator (PA) by Sertoli cells in stages VII and VIII of the rat seminiferous epithelial cycle is influenced by hormones and adjacent spermatogenic cells. To understand this interaction more in detail, we have analyzed the effects of FSH, (Bu)2cAMP, testosterone, insulin, and retinoic acid (RA) on staged seminiferous tubule segments in vitro. FSH stimulated stages VIIcd to XI of the cycle; similar results were obtained with (BU)2cAMP. RA stimulated PA secretion in stages I-VIIab, but testosterone and insulin had no effect in any stage. The secreted PA was mainly of the urokinase type, although small amounts of the tissue-type PA were found after stimulation by FSH and cAMP. These results suggest that spermatogenic cells modify the responsiveness of Sertoli cells to hormonal stimulation. Stages I-VIIab are sensitive to stimulation by RA whereas stages VIIcd-XI are preferentially stimulated by FSH and (Bu)2cAMP.
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PMID:Stage-specific regulation of plasminogen activator secretion in the rat seminiferous epithelium. 302 24

Selected variables of the fibrinolytic system were assessed in 23 men with insulin-treated diabetes with no measurable pancreatic beta-cell function. Gliclazide, a second-generation sulphonylurea drug, was administered to the patients over a period of 6 months in daily doses of 160 mg or 240 mg, and blood samples were obtained before, during, and after treatment. Determined by global assays, the drug did not significantly change plasminogen activator activities in euglobulins. Measurements of specific components of the system of fibrinolysis showed a marginal increase during administration of gliclazide of tissue-type plasminogen-activator antigen and prekallikrein activity in plasma, whereas the activities in euglobulins of the intrinsic plasminogen proactivators remained nearly the same during the study. Levels in plasma and euglobulin of C1-inactivator antigen and in plasma of factor XII antigen and t-PA inhibition capacity remained constant throughout the study. There were no changes of the increase in concentration of t-PA activity and t-PA antigen following venous occlusion. The metabolic state remained the same during the whole study. It is concluded that gliclazide induces small, but significant, non-insulin-dependent extrametabolic effects on the extrinsic (t-PA) and intrinsic (prekallikrein) system of fibrinolysis. Whether these changes are of physiological importance remains to be demonstrated.
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PMID:Effects of an oral antidiabetic drug on the fibrinolytic system of blood in insulin-treated diabetic patients. 305 Mar 64

This study was undertaken to obtain further information on the mechanism by which blood fibrinolytic activity, a balance between plasminogen activators and inhibitors, is lowered in obese subjects. Fasting blood samples were collected from 35 subjects, aged 15 to 45 years, with normal glucose tolerance and a Body Mass Index (BMI) varying widely between 16 and 45 (normal, 19 to 25). Euglobulin Fibrinolytic Activity (EFA) did not correlate with the level of tissue type plasminogen activator (t-PA) related antigen but exhibited a negative correlation with the level of PA inhibitor (r = -.609, P less than 0.01). EFA was negatively and PA inhibitor positively correlated with both BMI (r = -.381, P less than 0.02 and .664, P less than 0.01, respectively) and plasma insulin level (r = .410, P less than 0.02 and .521, P less than 0.01, respectively). Stepwise analysis showed that these correlations were independent. As expected, plasma insulin was correlated with BMI (r = .512, P less than 0.01) and triglyceride level (r = .38, P less than 0.02), total cholesterol with age (r = .379, P less than 0.02). Ten obese subjects were submitted to a 24-hour fast. While body weight did not change appreciably, plasma insulin decreased from 22.3 +/- 2.2 to 16.3 +/- 1.1 microU/ml, EFA increased from 3.6 +/- .8 to 4.9 +/- .67 mm, and PA inhibitor decreased from 4.52 +/- .76 to 3.44 +/- .63 IU/mL. All these differences were significant. T-PA-related antigen did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. 308 78


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