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)

Blood pressure (BP), plasma prekallikrein (PK), and the extent of activation of factor XII (XII-ACT) were studied after the intravenous injection into rats of dextran (Macrodex), the ionic radiographic contrast substance iodipamide (Biligrafin), or the non-ionic contrast substance iohexol (Omnipaque). After acetone activation plasma kallikrein was assayed as plasminogen activator, BAEe esterase or S-2302 amidase, and factor XIIa was assayed as kaolin-activated prekallikrein activator. Dextran induced a strong and lasting hypotension, preceded by significant lowerings in PK and XII-ACT. Iodipamide induced a rapid and dose dependent BP fall, no change in plasma PK, but a slightly reduced XII-ACT. Iohexol induced no significant alterations, neither in BP, nor in plasma parameters. Pretreatments of the rats with iodipamide abolished the dextran-induced reductions in PK and XII-ACT, and almost blocked the fall in BP. We conclude that the ionic contrast substance iodipamide is capable of blocking dextran shock in the rat by preventing an activation of the contact activating system in plasma.
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PMID:Effects of intravenous radiographic contrast media on the blood pressure and on factors of the contact activation system in the rat. 243 54

Human monocytes/macrophages produce plasminogen activator-specific inhibitors (PAIs) that form covalent complexes with urokinase-type plasminogen activator (uPA). We have characterized two functionally and antigenically related forms of PAIs produced by resting and phorbol myristate acetate (PMA)-treated U 937 cells: an Mr 40,000 form, presumably nonglycosylated, with a pI of 5.2, that is constitutively synthetized by these cells and that remains predominantly intracellular; a PMA-induced form of heterogeneous Mr (50,000-65,000) with a pI of 4.7, that is preferentially secreted; this PAI is glycosylated with terminal sialic acid residue(s). Biosynthetic labeling experiments demonstrated that both PAIs are synthetized by U 937 cells. They are inactivated upon treatment with propanol, heat, and acid; the covalent and equimolar complexes formed between these PAIs and 125I-uPA are dissociated by ammonium hydroxide, suggesting that the PAIs are linked to uPA via an ester bond. Human peripheral blood monocytes/macrophages also produce the two forms of PAI. These PAIs are clearly different from the main plasma protease inhibitors and they are both antigenically related to the PAI-2 characterized in human placenta.
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PMID:Plasminogen activator-specific inhibitors produced by human monocytes/macrophages. 243 95

Recent studies conducted in our laboratory have demonstrated that plasminogen activator (PA) is present in granulosa cells collected from the largest preovulatory follicle in the ovary of the domestic hen, and that its activity can be modulated by a variety of hormones in vitro. The present study was conducted to evaluate the intracellular mechanisms involved in the control of hen granulosa cell PA activity through the use of physiological and pharmacological agents. Treatment of granulosa cells with increasing doses (1, 10, and 50 ng/tube) of ovine LH resulted in a significant reduction of PA activity, which was accompanied by an increase in intracellular levels of cAMP. Furthermore, the effects of LH were potentiated by cotreatment with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 mM). Exposure of cells to increasing concentrations of the adenylyl cyclase activator forskolin (0.005, 0.01, 0.05, and 0.1 mM) resulted in a significant reduction in PA activity at all doses given. Similarly, the presence of the cAMP analog 8-bromo-cAMP (0.005, 0.01, 0.05, 0.1, 0.5, 1.5, and 10 mM) caused a dose-dependent inhibition of PA activity from 0.005 to 1.0 mM, further suggesting the involvement of cAMP in the inhibitory regulation of hen granulosa cell PA activity. The induction of intracellular calcium mobilization through the use of the calcium ionophore A23187 (0.1, 0.5, 1, and 2 microM) resulted in a dose-dependent suppression of PA activity. By contrast, treatment of granulosa cells with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA; 0.5, 5, 10, 25, and 50 micrograms/tube), a compound that activates protein kinase-C, stimulated PA activity in a dose-dependent fashion; a non-tumor-promoting phorbol ester (phorbol 13-monoacetate; 0.5, 10, and 50 ng/tube) was without effect. Coincubation of granulosa cells with a submaximal dose of PMA (5 ng/tube) and low concentrations of A23187 (0.001, 0.005, 0.01, and 0.05 microM) could not significantly enhance the stimulatory effects of PMA on PA activity; however, higher concentrations of the ionophore (0.1, 0.5, and 1.0 microM) completely abolished PMA-stimulated PA activity. The stimulatory effects of PMA could also be eliminated by cotreatment with a protein kinase-C inhibitor (H-7; 100 microM), a mRNA transcription blocker (actinomycin-D; 5 micrograms/tube), or a protein synthesis inhibitor (cycloheximide; 50 micrograms/tube).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of a phorbol ester, a calcium ionophore, and 3',5'-adenosine monophosphate production on hen granulosa cell plasminogen activator activity. 245 14

Medroxyprogesterone acetate (MPA) is an anti-cancer drug for mammary carcinomas and an angiostatic steroid. The effects of MPA on the growth and plasminogen activator (PA) activity of bovine endothelial cells were investigated to elucidate the inhibitory mechanism observed in angiogenesis. MPA did not suppress the growth of capillary endothelial cells, even at high concentrations. On the other hand, in bovine endothelial cells of 3 types (adrenal cortical capillary, aortic and pulmonary artery endothelial cells), MPA inhibited extracellular and cell-associated activity of PA, which might be a protease involved in the neovascular response. MPA also greatly inhibited the high level of PA induced by basic fibroblast growth factor (FGF). The same result was obtained when PA production was induced by 4 beta-phorbol-12-myristate-13-acetate (PMA) in endothelial cells. These findings suggest that one of the points of inhibitory action of MPA in the process of angiogenesis may be the suppression of PA activity, and that inhibition of this protease might be useful for reduction of tumorigenic or excessive angiogenesis in vivo.
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PMID:Medroxyprogesterone acetate, an anti-cancer and anti-angiogenic steroid, inhibits the plasminogen activator in bovine endothelial cells. 247 7

Current studies show a more than 50-fold variation in the estimated level of tissue-type plasminogen activator (t-PA) activity in normal resting blood samples that result from major differences in the methods used to sample, preserve, and assay t-PA activity in blood. In this study we developed optimized methods for stabilizing and measuring t-PA activity in plasma by using a coupled plasminogen-chromogenic substrate (amidolytic) assay. To maximize the recovery of t-PA activity, blood should be acidified within 60 seconds after being drawn by adding 2 parts whole blood to 1 part 0.5 mol/L sodium acetate, pH 4.2. This method prevents hemolysis and eliminates 70% of the alpha 2-plasmin inhibitor. Optimum conditions for measuring t-PA activity are pH 8.0 to 8.3 (37 degrees C), ionic strength 0.02 to 0.04, 0.5 mumol/L plasminogen, 80 micrograms/ml CNBr-cleaved fibrinogen, and a chromogenic substrate concentration of 0.65 mmol/L D-valyl-leucyl-lysyl-p-nitroanilide, 0.25 mmol/L D-valyl-phenylalanyl-lysyl-p-nitroanilide, or 0.2 mmol/L D-norleucyl-hexahydrotyrosyl-lysyl-p-nitroanilide. The final assay is linear with respect to added one-chain t-PA, two-chain t-PA, and acidified plasma. There was no difference in t-PA activity measured with ethylenediaminetetraacetic acid anticoagulant versus that measured with citrate anticoagulant after correction for dilution effects (average resting t-PA activity in plasma from 20 healthy individuals = 1.59 IU/ml). We conclude that assay conditions can have major effects on the measurement of t-PA activity in plasma and that suboptimal conditions may result in a significant underestimation of t-PA activity.
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PMID:Optimum conditions for the stabilization and measurement of tissue plasminogen activator activity in human plasma. 249 79

Urokinase-type plasminogen activator, a neutral proteinase, seems to play a central role in the degradation of the extracellular matrix that accompanies a number of biological phenomena including inflammatory reactions and neoplasia. The effect of auranofin and retinoic acid on the plasminogen activator activity expressed by two cell types, i.e. murine macrophages and Lewis lung carcinoma cells, has been investigated. Low concentrations of both drugs (10(-6)-10(-7) M) can inhibit in vitro the induction of plasminogen activator in macrophages stimulated by phorbol 12-myristate 13-acetate. This action occurs rapidly (15 min), is irreversible and is independent of a global cytotoxic effect. Auranofin and retinoic acid remain without effect in macrophages when added after stimulation by the phorbol ester. Both drugs are thus potent inhibitors of the induction of plasminogen activator activity in macrophages, possibly through an interaction with the protein kinase C system. The plasminogen activator activity of Lewis lung carcinoma cells, which is apparently not dependent on a protein kinase C pathway, is not influenced by auranofin or retinoic acid. These observations may contribute to explain: (1) the activity of auranofin and retinoic acid in rheumatoid arthritis, and (2) the antitumor promoting activity of retinoic acid. It would be relevant to assess whether auranofin may exhibit, like retinoic acid, an antitumor-promoting activity.
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PMID:Comparison of the effects of auranofin and retinoic acid on plasminogen activator activity of peritoneal macrophages and Lewis lung carcinoma cells. 250 Jan 27

The secretion of tissue plasminogen activator (t-PA), urokinase (u-PA) and their inhibitors by the human leukemia cell line K562 was examined. K562 cells normally secrete both t-PA and u-PA in a ratio of 3:1. After addition of 10 or 1 ng/mL phorbol myristate acetate (PMA) to K562 cells, a marked decrease in enzymatic activity is observed in the medium. However, when t-PA antigen rather than activity is measured, an increased amount is found in the medium under these conditions. PMA also induces secretion of the two inhibitors of plasminogen activator: plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2). This accounts for the decrease in total enzymatic activity under conditions when production of t-PA antigen is increased. A study of the time course of induction revealed that the synthesis of plasminogen activator occurred before that of its inhibitors. Low concentrations of PMA (0.1 ng/mL) induce t-PA antigen primarily and not the inhibitors. This results in an increase in total enzymatic activity, with 94% of the secreted activity being t-PA. Thus, the secretion of plasminogen activators and their inhibitors can be manipulated in certain leukemic cells by inducers such as PMA.
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PMID:Regulation and secretion of plasminogen activators and their inhibitors in a human leukemic cell line (K562). 250 6

Human SH-SY5Y neuroblastoma cells treated with retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or nerve growth factor differentiated morphologically to neuronlike cells with increased amounts of neurofilament protein and mRNA. All three effectors induced an increase in the amount of relative molecular weight (Mr) 70,000 tissue-type plasminogen activator (t-PA) and its mRNA, as determined by immunocapture, enzyme activity, and Northern blotting analyses. About 90% of the t-PA activity was secreted to the culture medium. In contrast, of the three effectors studied, only TPA induced transcription of the proto-oncogene c-fos, studied as a control gene responsive to various stimuli, and induced a rapid increase in urokinase-type PA (u-PA). Most of the u-PA activity induced by TPA remained cell-associated. Because induction of differentiation correlated closely with induction of t-PA, and not u-PA, the authors propose that t-PA may have a functional role in the morphological differentiation of neuronal cells.
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PMID:Induction of morphological differentiation of human neuroblastoma cells is accompanied by induction of tissue-type plasminogen activator. 250 35

The fibrinolytic enzyme profile of SMS-KAN human neuroblastoma cells was found to vary dramatically during the differentiation process. Five maturational agents--retinoic acid, dibutyryl cAMP, 5-bromodeoxyuridine, sodium butyrate and phorbol myristate acetate were tested for their effects on cellular morphology, DNA synthesis, plasminogen activator (PA) and PA inhibitor (PAI) activity. SMS-KAN cells secrete urokinase (UK) and tissue PA (tPA) as well as a possibly unique PAI. Treatment of cells with 1 microM RA resulted in an inhibition of proliferation, extension of neurite-like processes indicative of differentiation, as well as a switch from secretion of UK to tPA and a reduction in PAI secretion. Other agents which caused neural process formation and decreased cell proliferation also induced alterations in PA/PAI while agents which had no detectable effect on cell growth induced little change in the fibrinolytic enzyme profile.
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PMID:Alterations in plasminogen activator and inhibitor activity during the differentiation of a human neuroblastoma cell line, SMS-KAN. 253 81

Recent reports suggest that epidermal growth factor (EGF) or related peptides may act as local hormones to regulate granulosa cell differentiation. While FSH and GnRH are known to stimulate accumulation of tissue-type plasminogen activator (tPA) mRNA in granulosa cells, studies using nonovarian cells have shown stimulation of tPA by EGF. In this study, the effect of EGF and its structural analog transforming growth factor-alpha (TGF alpha) on ovarian tPA mRNA and activity was investigated. Granulosa cells obtained from immature estrogen-treated rats were cultured with FSH or increasing doses of EGF or TGF alpha before analysis of tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by a fibrin overlay technique. Like FSH and GnRH, EGF and TGF alpha stimulated the secretion of tPA activity in a dose- and time-dependent manner (onset, 12 h; maximum, 48 h). Northern blot hybridization of total RNA using a rat cRNA probe for tPA showed the accumulation of a 22S species mRNA in cells treated with EGF or TGF alpha, but not with nerve growth factor, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells confirmed a time-dependent increase in tPA mRNA preceding that in enzyme activity. Cotreatment of a saturating dose of EGF with phorbol myristate acetate (PMA) or GnRH resulted in additive increases in both tPA enzyme activity and mRNA levels. In addition, pretreatment with PMA desensitized the cells to subsequent treatment with PMA or GnRH, but did not diminish EGF-induced tPA mRNA, suggesting that EGF acts through a pathway independent of protein kinase-C. Also, extracellular cAMP levels did not increase with EGF treatment in the presence or absence of a phosphodiesterase inhibitor, suggesting the lack of involvement of the protein kinase-A pathway. Suppression of protein synthesis by cycloheximide inhibited the induction of tPA mRNA by EGF, whereas similar treatment resulted in the superinduction of tPA mRNA in FSH-treated cells, suggesting that EGF and FSH do not share the same pathway. These results suggest that EGF and TGF alpha induce tPA mRNA and activity in granulosa cells through a pathway independent of protein kinases-A (FSH) and -C (GnRH and phorbol ester), providing an interesting model for future elucidation of the molecular mechanism involved in tPA gene expression.
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PMID:Epidermal growth factor stimulates tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells: mediation by pathways independent of protein kinases-A and -C. 254 97


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