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)

Sertoli cells (SC), plated onto an extracellular matrix-coated membrane mounted in a two-chambered assembly, secrete both transferrin and plasminogen activator (PA) into each chamber. Although transferrin concentrations are greatest in the inner chamber, concentrations of PA activities in the outer chamber are equal to or higher than those in the inner chamber. These data indicate that transferrin and PA are preferentially secreted in different directions. The addition of FSH or cAMP derivatives stimulates the formation and secretion of tissue-type PA. Addition of FSH enhances the polarized secretion of PA into the outer chamber, as measured by elevated ratios of outer to inner compartment PA concentrations. Ratios of PA to transferrin concentrations in the outer compartment are also increased in FSH-treated preparations, demonstrating that the differential secretion of the two products is enhanced by FSH. We interpret these data to indicate that polarized SC preferentially secrete transferrin apically while preferentially secreting PA basally, and that FSH augments this polarity of SC maintained in the two-chamber assembly. The addition of peritubular cells to the system results in decreased levels of total PA activity, with greatest diminution evident in the outer compartment. Data are consistent with previous observations that peritubular cells decrease PA activity by secreting a specific inhibitor of PA. Measurements of relative amounts of transferrin and PA secreted into inner and outer chambers, respectively, provide a means to evaluate the tightness of the seminiferous tubule barrier in the model system and the extent of polarized secretion by SC in the two-chambered assembly.
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PMID:Control of levels of plasminogen activator activity secreted by Sertoli cells maintained in a two-chamber assembly. 245 45

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

At present, there is a lack of availability of differentiation markers for colon carcinoma. This may, in part, be a consequence of the diversified function of the normal human colon. This study addresses the possibility that the expression of urokinase and its receptor is inversely related to differentiation in colon carcinoma. Six colon carcinoma cell lines including three well-differentiated (CBS, GEO, FET) and three poorly differentiated ones (HCT116, HCT116b, RKO) were screened for urokinase receptor display and secretion of the plasminogen activator. A radioreceptor assay was used to determine receptor levels. Binding of radioactive urokinase to colon cells was saturable, specific, and time dependent. Cell-bound 125I-labeled protease was unaffected by the presence of epidermal growth factor, low-molecular-weight urokinase, plasminogen, or transferrin. Time course studies revealed that maximum amounts of radioactive tracer were bound in a 30-min period with no change occurring over the course of a 90-min incubation. Scatchard analysis of ligand binding indicated that the well-and poorly differentiated cells could be separated on the basis of receptor display; the aggressive RKO, HCT116, and HCT116b expressed in excess of 10(5) sites per cell, while the more indolent CBS, GEO, and FET possessed less than 1.5 X 10(4) receptors per cell. The colon carcinoma cells were also analyzed for urokinase in the conditioned medium. Low levels of the plasminogen activator (0.8 to 1.3 ng/ml/10(6) cells/72 h) were associated with the more "mature" cells. This was in contrast to the elevated levels of the protease (3.9 to 11.4 ng/ml/10(6) cells/72 h) present in the medium derived from the more aggressive cells (HCT 116, HCT116b, RKO). Thus, secreted urokinase and/or the expression of cellular receptor for the plasminogen activator may provide useful measurements of the degree of undifferentiation of in vitro colon carcinoma.
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PMID:Determination of the levels of urokinase and its receptor in human colon carcinoma cell lines. 283 52

The effect of delta-9-tetrahydrocannabinol (THC) on rat Sertoli cell function was investigated. THC significantly increased ABP secretion by 1.5- to 2.1-fold but did not consistently enhance the stimulation of ABP induced by FSH, testosterone or dibutyryl cyclic AMP. ABP was measured by steady-state polyacrylamide gel electrophoresis, DEAE Bio-Gel and immunoassay; all three methods gave similar results. The minimal concentration of THC that stimulated ABP was 10 ng/ml; maximal stimulation was observed with 100-200 ng/ml. This effect was specific since THC did not affect gamma glutamyl transpeptidase activity or the secretion of plasminogen activator, lactate and transferrin. This observation that THC affects ABP secretion specifically is the first report of any differential effect of a drug on Sertoli cell secretion.
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PMID:Delta-9-tetrahydrocannabinol stimulates ABP secretion from rat Sertoli cells in vitro. 287 Dec 32

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

A simplified procedure for the production and purification of human tissue-type plasminogen activator (t-PA) is described. Bowes-melanoma cells were maintained in continuous serum-free culture. The cell nutrient consisted of Dulbecco's modified Eagle's medium (DMEM) supplemented with insulin (5 mg/litre), transferrin (5 mg/litre), progesterone (1 nM), cortisol (10 nM), aprotinin (2 X 10(4) units/litre) and a mixture of trace elements. t-PA accumulated in the culture medium at a rate of 40 units/day per ml and was harvested every third day. Cell losses during each harvest, leading to a steady decline of enzyme yields, were compensated for by treating the cells with 5% (v/v) fetal-bovine serum in DMEM every 6-8 weeks. t-PA was rapidly purified by a combination of cation-exchange chromatography and gel filtration. The procedure yielded mainly single-chain t-PA of a specific activity of 80 000 to 100 000 units/mg.
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PMID:Human tissue-type plasminogen activator. Production in continuous serum-free cell culture and rapid purification. 403 34

This paper reports the growth and differentiation of the mouse embryonal carcinoma cell line F9 in completely defined culture media. The defined growth medium, referred to as EM-3, contains plasma fibronectin, insulin, and transferrin in place of serum. F9 cells cultured in EM-3 for over 15 generations retain their ability to form tumors and to differentiate. Fibronectin is essential for the attachment of F9 cells in defined media and its effect can be blocked with affinity-purified anti-fibronectin. When retinoic acid was added to EM-3, the F9 cells differentiated. The majority of the the newly formed cells differed from patient F9 cell two major respects: (i) they were morphologically different; and (ii) they secreted plasminogen activator, and the secretion was stimulated by dibutyrlyl adenosine cyclic monophosphate.
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PMID:Growth and differentiation of embryonal carcinoma cell line F9 in defined media. 624 61

The effect of retinoic acid on the synthesis and degradation of basement membrane components by endoderm cells derived from mouse embryonal carcinoma (EC) cells was studied in a serum-free, defined medium. By immunofluorescence these cells accumulate type IV collagen, laminin, and fibronectin after growth in media containing epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin, transferrin, and Pedersen fetuin. Collagen accounted for 2 to 4% of the newly synthesized proteins, of which 90% were found in the culture media. This collagen was identified as Pro-type IV be gel electrophoresis and enzymatic susceptibility. The EC cells preferentially attached to type IV collagen in vitro and such attachment was mediated by laminin. Treatment of EC cells with retinoic acid caused an increased accumulation of collagen (10 to 15% of secreted proteins) and also stimulated the elaboration of latent protease which degraded laminin and type IV collagen. The laminin-degrading activity was plasminogen dependent. The type IV collagen-degrading activity was a metal protease which could be activated by trypsin or plasmin. It is likely that at least part of the laminin degrading activity is plasmin (mediated through plasminogen activator), since highly purified plasmin is shown to degrade native laminin.
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PMID:Stimulation of retinoic acid of synthesis and turnover of basement membrane in mouse embryonal carcinoma-derived endoderm cells. 628 41

Two unrelated multipotent embryonal carcinoma cell lines, OC-15S1 and 1003, have been cultured in hormone-supplemented defined media in order to identify the signals that influence their differentiation. Previous studies have shown that F9 embryonal carcinoma cells can be grown for many generations in the defined medium, EM-3, which contains fibronectin, insulin, and transferrin in place of serum. F9 cells, which only differentiate into a few cell types, undergo little or no differentiation in EM-3 unless an inducer is present (A. Rizzino and C. Crowley, 1980, Proc. Nat. Acad. Sci. USA 77, 457-461). This report demonstrates that, in contrast to F9, OC-15S1 and 1003 embryonal carcinoma cells do not proliferate in EM-3. Instead, the cells differentiate. However, the differentiated cells do not survive in EM-3 unless it is supplemented with factors such as purified serum lipoproteins. In EM-3 containing high-density lipoprotein, a population of differentiated cells, devoid of embryonal carcinoma cells, is formed. The differentiated cells that appear exhibit an epitheloid morphology throughout the culture. These cells also secrete plasminogen activator and two different criteria argue that it is the type released by parietal endoderm. This suggests that, under the influence of the defined medium, both multipotent embryonal carcinoma cell lines differentiate at high frequency into parietal endoderm. It was also determined that fibronectin promotes the differentiation of OC-15S1 and 1003 in serum-containing media, and this suggests that fibronectin is at least partly responsible for the differentiation observed in EM-3 plus high-density lipoprotein. In light of these findings, it is suggested that fibronectin may directly influence cellular differentiation during early mammalian development.
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PMID:Two multipotent embryonal carcinoma cell lines irreversibly differentiate in defined media. 668 83


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