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)

Expression vectors containing the pro-urokinase (pro-UK) cDNA (pSV2-proUK) and a dihydrofolate reductase cDNA (pSV2-dhfr or MMTV-dhfr) were cotransfected into CHO-dhfr- cells by the calcium phosphate precipitation technique. The dhfr+ transformants were selected by fibrinolytic agarose plate assay. Two colonies, named CLF-14 and CLF-8, exhibited significantly high expression levels of the biological activity of urokinase-type plasminogen activator (mu-Pa). They reached more than 24 IU/10(6) cells/48 h and 16 IU/10(6) cells/48 h, respectively. Examination of the cell supernatants for mu-Pa antigenicity using ELISA method also showed strong positive results, and the quantities of expression were about 0.14-0.22 micrograms/10(6) cells/48 h and 0.08-0.14 micrograms/10(6) cells/48 h, respectively. The mu-Pa secreted by stable transformed cells could be completely inhibited by UK anti-serum, but not by tissue-type plasminogen activator (t-PA) antiserum nor by normal rabbit serum.
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PMID:Expression of pro-urokinase cDNA in Chinese hamster ovary cell line. 180 21

Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity.
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PMID:Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism. 182 12

Calcitriol-induced differentiation of U937 mononuclear phagocytes is known to have divergent effects on the synthesis of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2). In this study, we sought to determine whether calcitriol affects the expression of these proteins by modulating intermediate signal transduction involving intracellular calcium and protein kinase C (PKC). U937 cells were stimulated with calcitriol (50 nM) for 6-72 hr, inducing a transient increase in specific binding of [3H]phorbol dibutyrate ([3H]PDBu), seen only after 24 hr. Staurosporine (2 nM), a PKC inhibitor, had no effect on calcitriol-induced secretion of plasminogen activator (PA) activity. However, staurosporine significantly (P less than 0.05) inhibited the ability of calcitriol to enhance phorbol myristate acetate (PMA)-induced secretion of PA inhibitor activity, indicating that this priming effect of calcitriol requires expression of PKC. The calcium ionophore A23187 (0.1 microM) induced a modest increase in secreted PA inhibitor activity, in contrast to the secretion of PA activity which is consistently seen in response to calcitriol. Northern blot analysis demonstrated that A23187 induced an increase in PAI-2 mRNA and a marked reduction in uPA mRNA, while calcitriol induced opposite changes in both mRNA species. We conclude that calcitriol modulates uPA and PAI-2 expression by multiple mechanisms that are both PKC dependent and PKC independent. Our studies also demonstrated that increased intracellular calcium alters the synthesis of both uPA and PAI-2 in a manner which favors expression of PA inhibitor activity.
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PMID:Calcitriol-mediated modulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-2. 190 5

Previous studies have shown that tissue-type plasminogen activator (t-PA) in blood is cleared by the liver partially through a mannose-specific uptake system. The present study was undertaken to investigate, in a purified system, whether t-PA is recognized by the mannose receptor which is expressed on macrophages and liver sinusoidal cells. The mannose receptor was isolated and purified from bovine alveolar macrophages and migrated as a single protein band at Mr 175,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Ligand blotting revealed that this protein specifically bound t-PA. The t-PA-receptor interaction was further characterized in a binding assay, which showed saturable binding with an apparent dissociation constant of 1 nM. t-PA binding required calcium ions and was negligible in the presence of EDTA or at acid pH. Mannose-albumin was an effective inhibitor, whereas galactose-albumin did not have a significant effect. From a series of monosaccharides tested, D-mannose and L-fucose were the most potent inhibitors, N-acetyl-D-glucosamine was a moderate inhibitor, whereas D-galactose and N-acetyl-D-galactosamine were ineffective. t-PA, deglycosylated by endoglycosidase H, did not interact with the receptor. It is concluded that the mannose receptor specifically binds t-PA, probably through its high mannose-type oligosaccharide.
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PMID:Binding of tissue-type plasminogen activator by the mannose receptor. 190 88

Proteose peptone (p.peptone) remarkably induced tissue plasminogen activator (t-PA) activity in the conditioned medium of confluently cultured human embryonic lung diploid fibroblast, IMR-90 cells, in a dose-dependent manner. t-PA activity correlated well with the amount of t-PA antigen found in the conditioned medium of IMR-90 cells stimulated by p.peptone. t-PA production by IMR-90 cells stimulated by p.peptone was dependent on extracellular Ca2+ concentration and maximum t-PA production required approximately 3.6 mM extracellular Ca2+. Conversely, elimination of Ca2+ from the culture medium by EGTA, Ca2+ chelate agent, strongly inhibited t-PA production induced by p.peptone. t-PA production induced by p.peptone was inhibited in a dose-dependent manner by Verapamil, which inhibits Ca2+ uptake through the slow channels and also by W-7, an inhibitor of calmodulin. These results suggested that influx of extracellular Ca2+ into IMR-90 cells was caused by p.peptone and induced t-PA production by the cells.
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PMID:Role of Ca2+ in t-PA production by human embryonic lung diploid fibroblast, IMR-90 cells, stimulated by proteose peptone. 190 95

In perfused rat hindlegs, platelet-activating factor and bradykinin induced the acute release of both tissue-type plasminogen activator (t-PA) and von Willebrand Factor (vWF). The time course of release was similar for both proteins, and the amounts of t-PA and vWF released under various conditions were closely correlated. Release of both t-PA and vWF required extracellular calcium, and could be induced by the calcium ionophore A-23187. Protein synthesis was not required for release to occur. Phorbol myristate acetate also induced release of t-PA and vWF, though with a different time course; DDAVP was inactive. The results suggest that the release of t-PA, and that of vWF, are closely linked at the cellular level.
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PMID:The simultaneous acute release of tissue-type plasminogen activator and von Willebrand factor in the perfused rat hindleg region. 211 27

The effect of human activated protein C (APC) on fibrinolysis was studied in a cell-free system by continuously monitoring the thrombin-induced formation and subsequent tissue-type plasminogen activator-induced degradation of fibrin. In systems comprising dialyzed human plasma, APC shortens the time for lysis to occur in a concentration-dependent, saturable manner. Half-maximal activity occurs at an APC concentration of 10 nM. The effect is mediated by enhanced plasminogen activation and is dependent upon ionized calcium. The effect is lost when plasma adsorbed with barium citrate is utilized in place of unadsorbed plasma. The effect can be reconstituted, however, from components recovered from the barium citrate precipitate. Fractionation of the barium citrate adsorbable proteins with polyethylene glycol (PEG) provides two fractions, one of which is obtained by precipitation at 5% PEG, and the other of which is obtained from the 5% PEG supernatant by further precipitation at 40% PEG. The latter fraction contains Factor X and presumably the other vitamin K-dependent clotting factors. Both of these fractions together, but neither of them alone, fully reconstitute barium-adsorbed plasma, such that APC-enhanced fibrinolysis occurs as in non-adsorbed plasma. These fractions also are sufficient to provide for an APC effect in a system in which purified plasminogen and fibrinogen are used in place of barium citrate-adsorbed plasma. Thus, an effect of APC on tissue-type plasminogen activator-induced fibrinolysis exists which is Ca2(+)-dependent and requires two or more, as yet unidentified, components that can be precipitated from human plasma by barium citrate.
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PMID:The activated protein C-mediated enhancement of tissue-type plasminogen activator-induced fibrinolysis in a cell-free system. 212 Feb 9

Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris. 212 Oct 16

PtdIns liposomes, at a concentration of 40 microM, induced in FLF the synthesis of t-PA-Ag, and enhanced 45Ca2+ uptake. The induction of t-PA-Ag biosynthesis by PtdIns liposomes in FLF was inhibited by 5-15 microM verapamil, an inhibitor of Ca2+ uptake via the so-called "slow channels" by 0.5-10 microM TFP, an inhibitor of Ca2+ transport ATPase, and by 10-90 microM TMB-8, an inhibitor of intracellular Ca2+ mobilization. t-PA-Ag secretion was inhibited by decreasing the Ca2+ concentration less than 1.2 mM. On the other hand, addition of 0.08 microM of calcium ionophore A23187 increased t-PA-Ag biosynthesis after 72 hr of incubation by 247% (P less than 0.01). These data support previous results and indicate that the synthesis of t-PA in FLF is Ca2+ dependent. Thus, it is suggested that PtdIns liposomes increase t-PA biosynthesis by affecting calcium metabolism.
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PMID:Phosphatidylinositol liposomes increase calcium uptake and tissue plasminogen activator secretion by fetal human lung fibroblasts. 212 30

Stimulation of the isolated perfused rat hindleg vascular bed with various concentrations of endothelin-1 or endothelin-3 resulted in the acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF). The release of both endothelial cell products required the presence of extracellular calcium; the release of vWF by endothelin was instantly inhibited by disodium EDTA. The calcium antagonists nifedipine, diltiazem and verapamil partially inhibited endothelin-induced t-PA release, but had no effect on endothelin-induced vWF release.
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PMID:Endothelin-1 and -3 induce the release of tissue-type plasminogen activator and von Willebrand factor from endothelial cells. 212 63


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