Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell-derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours. Plasminogen activator was infused at a rate of 500 IU X kg-1 X min-1 for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4, 5 and 6 hours, with 7.7 +/- 1.5 X 10(-3) IU X mg protein-1 (n = 8) in the plasminogen activator group versus 17.8 +/- 3.5 X 10(-3) IU X mg protein-1 (n = 7) in the vehicle group at 6 hours (mean +/- SEM). The area at risk in the two ischemic groups was not different, being 14.6 +/- 1.5 and 16.6 +/- 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 +/- 3.9% of the area at risk compared with 46.8 +/- 4.2% of area at risk in cats receiving only the vehicle (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats. 308 17

The influence of ethinylestradiol and the three natural estrogens, i.e. estrone, 17-beta-estradiol and estriol, was studied in a melanoma cell line producing a tissue-type plasminogen activator (t-PA). The cell cultures were exposed to the four estrogens by addition of the steroids dissolved in a weak alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. Ethanol (0.76% w/v) stimulated the t-PA production, while no significant effect of the estrogens in the concentration of 1.7 X 10(-7) M was seen. By tenfold increase in estrogen concentration a highly significant reduction of t-PA levels was recorded in the cultures exposed to ethinylestradiol and 17-beta-estradiol. Estriol differed from these two estrogens in having rather weak inhibitory effect; whereas estrone in this concentration had toxic effect on melanoma cells. It was concluded that the present estrogens, in particular ethinylestradiol and 17-beta-estradiol, had a dose-dependent inhibitory effect on the production of t-PA in melanoma cell culture.
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PMID:Estrogen regulation of tissue plasminogen activator in a human melanoma cell line. 308 11

Phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate) stimulates the secretion of tissue-type plasminogen activator by the melanoma cell line, Bowes. This effect is associated with increased levels of mRNAs for both tissue-type plasminogen activator and a 48 kDa-protein. Labelling of melanoma cells with L-[35S]methionine allowed to identify an intracellular protein which, by 3 criteria, was identical with the in vitro translation product of the 48kDa-protein mRNA: a Mr of 48,000 on electrophoresis in the presence of sodium dodecyl sulphate; inducibility by phorbol ester and failure of reducing agents to affect electrophoretic mobility. As detectable by L-[35S]methionine labelling, the protein was mainly localized in the cytosol. In vitro phosphorylation reactions, carried out on subcellular fractions revealed a membrane-associated protein which also had the three characteristics of the aforementioned 48 kDa-protein. Phosphorylation did not require Ca2+-ions. Addition of phorbol ester to the reaction mixtures increased the phosphorylation. Reconstitution experiments between membrane and cytosol fractions of phorbol ester-treated and untreated cells showed that the 48kDa protein occurs in a cytosolic, unphosphorylated and a membrane-bound, phosphorylated form and that the former is converted to the latter by a phorbol ester activated, membrane-associated protein kinase.
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PMID:Phorbol ester stimulates the synthesis and phosphorylation of a 48 kDa-intracellular protein in plasminogen activator secreting melanoma cells. 308 56

Permanent cell lines (UCT-Mel 1 through 7) were established from biopsies of metastatic tissue taken from seven patients with malignant melanoma. Cells from these lines were all aneuploid and all grew as non-contact-inhibited, adherent monolayers. All of the lines, with the remarkable exception of UCT-Mel 6, formed tumours in nude mice, expressed the melanoma M-18 antigen and synthesized plasminogen activators exclusively of the tissue-type. UCT-Mel 6 cells were non tumourigenic, they lacked the M-18 antigen and they synthesized plasminogen activators exclusively of the urokinase type. UCT-Mel 1 and UCT-Mel 2 formed pigment in vitro and both of these lines showed an increase in pigment content and tyrosinase synthesis with increasing cell density. The rate of plasminogen activator released by UCT-Mel 1 and UCT-Mel 3 declined strikingly as the cells became confluent. Assuming that proteolytic activity is required for cell migration in vivo; that tyrosinase synthesis reflects expression of the differentiated phenotype and that melanoma cells retain some of the characteristics of neural crest cells, we suggest that the effects of confluence and close cell-cell contact provide a useful experimental counterpart for the study of normal neural crest all behaviour that is characterized by an inverse relationship between migration and a protease secretion on the one hand and pigmentation on the other.
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PMID:Characterization of seven human melanoma cell lines: melanogenesis and secretion of plasminogen activators. 309 Oct 56

A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was identical to that of tissue PA produced by Bowes melanoma cells. PA activity in human melanocyte culture medium was inhibited by anti-tissue PA IgG, but not by anti-urokinase IgG. Our results are the first to show that normal human melanocytes in culture secrete tissue plasminogen activator.
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PMID:Plasminogen activator secreted by cultured human melanocytes. 309 Oct 61

2 groups of healthy, informed volunteers were studied to assess tissue-type plasminogen activator (t-PA) inhibition in plasma of women using oral contraception (OC) and in normal women. The women in the 1st group (n=10, age range 21-30 years) had used a combined OC with 30 mcg ethinyl estradiol and 150 mcg levonorgestrel daily for 21 days per cycle for 4 months. They began using pills on the 7th day of their cycle. The 2nd group was made up of 15 women, age 20-28 years, with a regular menstrual cycle (range of 28-31 days) and with hormone levels within the normal range. None of the women had evidence of liver disease or active thrombotic disease, and none was taking other drugs. Blood samples were obtained in the morning with a minimum of stasis from an antecubital vein from fasting subjects in the supine position after a brief rest. The t-PA inhibition in plasma was determined by amidolytic titration with purified melanoma 2-chain t-PA. The measured inhibition was arbitrarily expressed in percentages relative to a pool of normal plasma. The t-PA activity was determined on fibrin plates as the activity measured in the presence of excess of C1-inactivator as described elsewhere. The mean levels of inhibition during the cycle were lower in the OC than in the normal group. The difference were statistically significant. When the separate sampling periods were compared, a statistically significant difference between the 2 groups were obtained for periods 2-5. There were only minor and insignificant fluctuations during the normal menstrual cycle. In the OC group the inhibition decreased from periods 1-5 with a statistical significance. Within both groups the fluctuations in t-PA inhibition were almost inversely related to the t-PA activities.
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PMID:Inhibition of tissue-type plasminogen activator in plasma of women using oral contraceptives and in normal women during a menstrual cycle. 309 96

Recombinant tissue-type plasminogen activator (rt-PA) from cultures of a genetically manipulated Bowes melanoma cell line (TRBM6) was purified in batches of average volume 451 using an autoclavable, reusable, continuous chromatography system comprising zinc chelate-Sepharose CL4B and lysine-Sepharose CL4B. After eight successive purifications the rt-PA was ultrafiltered to yield a preparation containing 4.9 mg protein/ml and 2.7 X 10(6) IU/ml. Analysis by SDS-polyacrylamide gel electrophoresis followed by staining with Coomassie brilliant blue R250 showed major protein bands at Mr = 63,000 and 65,000; most of the material was in the 1-chain form. The potential usefulness of a simple, rapid continuous chromatography system that can be operated under aseptic conditions is discussed.
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PMID:Large scale, rapid purification of recombinant tissue-type plasminogen activator. 310 Mar 25

Analysis of conditioned medium from three sublines of the B16 melanoma [F1 (parental), BL6 (invasive), F10 (metastatic)] by SDS-PAGE and zymography revealed the presence of plasminogen activator activity at 60,000 daltons. The relative activity was F10 greater than F1 greater than or equal to BL6. Treatment of the cells with the tumor promoter, phorbol myristate acetate (PMA) led to increased secretion of PA by F10 cells and a lesser increase in secretion by F1 cells and BL6 cells. In addition, a second plasminogen activator activity at 45,000 daltons was detected in conditioned medium from PMA treated F10 cells. Conditioned medium from F10 and F1 cells was also shown to contain a 33,000 dalton plasminogen activator binding protein. Upon PMA treatment the concentration of the binding protein increased in medium from F10 cells but not in similarly treated F1 cells. The binding protein, very likely a plasminogen activator inhibitor, was nearly undetectable in conditioned medium from control and PMA-treated BL6 cells. Therefore, the three sublines, which differ in in vivo phenotypic characteristics, also differ in their in vitro regulation of proteinase and proteinase inhibitor synthesis.
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PMID:Differences between the F10, BL6 and F1 sublines of the B16 melanoma in the enhancement of plasminogen activator and plasminogen activator inhibitor secretion by phorbol myristate acetate. 310 64

The influence of a protein-free and a protein-rich, supplemented serum-free medium on the production of plasminogen activator (t-PA) from Bowes melanoma cells was investigated in the Opticell culture system and compared to tissue culture flask cultures. In the presence of medium supplements metabolic activity and t-PA production were favoured in both systems. The addition of supplements was apparently more effective in the Opticell than in flask cultures, because t-PA activity obtained in the Opticell was 2-3 times higher in protein-rich medium, but 2 times lower in unsupplemented medium than in flasks. These results indicate that the protein content in a serum-free medium is important for product formation in the Opticell, and serum-free media which work at small scale in tissue culture flasks are not always suited for technical culture systems such as the Opticell but have to be adapted to them.
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PMID:Cultivation of Bowes melanoma cells in the Opticell system: influence of the addition of protein supplements to the serum-free medium on the production of plasminogen activator. 310 52

Interleukin 1, derived from human placenta, stimulates plasminogen activator activity in human articular chondrocytes. The stimulation of plasminogen activator activity can be abolished by preincubation of placental interleukin 1 with an antiserum to homogeneous 22K factor, a species of interleukin 1 beta, indicating that the stimulation of plasminogen activator activity is due to interleukin 1 and not contaminating factors. Chondrocytes produce three species of plasminogen activator, with apparent Mr approximately 50,000, 65,000 and 100,000 as determined after sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis with gels containing casein and plasminogen. Both placental interleukin 1 and 22K factor enhance the production of the species of Mr approximately 65,000 and 100,000. Comparison of the mobility of the plasminogen activator species on SDS-polyacrylamide gel electrophoresis with human urokinase (u-PA) and human melanoma tissue-type plasminogen activator (t-PA) and studies with antibodies to these enzymes indicate that the Mr approximately 50,000 species is a u-PA and the Mr approximately 65,000 a t-PA. The Mr approximately 100,000 species is possibly an enzyme-inhibitor complex. Interleukin 1 therefore appears to enhance the production of t-PA and a putative enzyme-inhibitor complex. Abolition of plasminogen activator activity in the fibrin plate assay with antibodies to t-PA and u-PA also confirms enhanced t-PA production on interleukin 1 stimulation, though there is also evidence for increased cell-associated production of u-PA.
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PMID:Interleukin 1 preferentially stimulates the production of tissue-type plasminogen activator by human articular chondrocytes. 310 96


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