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)

Euglobulin fibrinolytic activity of cyst fluid from six patients with aneurysmal bone cysys was considerably higher than that of arterial and venous blood of the corresponding patients. The high fibrinolytic activity was associated with a very low concentration of fibrinogen and a low concentration of plasminogen. Correspondingly, a high plasminogen activator activity was found in cyst tissue related to endothelial lining. It is suggested that fibrinolysis is an important factor in the maintenance and expansion of the aneurysmal bone cyst.
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PMID:Fibrinolytic activity in aneurysmal bone cysts. 120 38

The levels of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and t-PA/PAI-1 complex antigens were analyzed in the plasma of disseminated intravascular coagulation (DIC) patients and healthy controls. Other fibrinolytic parameters such as the levels of plasminogen, alpha 2-antiplasmin (alpha 2-AP), plasmin/alpha 2-AP (PAP), and D-dimer were also estimated to clarify the fibrinolytic states in these plasmas. The antigens of t-PA, PAI-1, and t-PA/PAI-1 complex were found to increase from 8.5 +/- 4.3, 54.4 +/- 21.2, and 8.6 +/- 3.5 ng/ml in normal plasma to 36.4 +/- 25.1, 106.8 +/- 54.7, and 46.6 +/- 34.5 ng/ml in DIC plasma, respectively. The molar ratio of total t-PA to total PAI-1 was 1:6 and 1:3 in normal plasma and DIC plasma, respectively, indicating an enhanced fibrinolytic state in the DIC plasma. The DIC plasma revealed a significant consumption of plasminogen (62.1 +/- 27.8%), and alpha 2-AP (63.7 +/- 25.3%) and an increase in PAP (2.6 +/- 2.7 micrograms/ml) and D-dimer (3.9 +/- 10.7 micrograms/ml). These results suggest that the production and secretion of t-PA and PAI-1 from endothelial cells were enhanced in DIC, resulting in an increased t-PA/PAI-1 complex with dominant fibrinolytic activity.
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PMID:Tissue-type plasminogen activator, type 1 plasminogen activator inhibitor and their complex in plasma with disseminated intravascular coagulation. 128 Mar 77

An increased blood fibrinolytic activity manifested by increased tissue plasminogen activator (t-PA) and decreased tissue plasminogen activator inhibitor (PAI-1) and increased FDP levels are seen in 40 patients with mild hypertrophy of prostate. Surgical treatment increased blood fibrinolytic activity manifested in the increase in t-PA, decrease in PAI-1, shortening of ELT, increase in FDP, and decrease in plasminogen and 2-AP activities. Blood fibrinolytic activity was the highest immediately after surgery with tendency to the gradual normalization. Positive ethanol test and decrease in thrombocyte count indicate and activation of blood clotting system induced by the tissue thrombo-elastins released during surgery. Subclinical DCI with the secondary increased fibrinolysis activation is present in patients with mild hypertrophy of the prostate both prior to and after surgery.
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PMID:[Tissue plasminogen activator, its inhibitor and other parameters of fibrinolysis in blood of patients operated for mild hypertrophy of the prostate]. 128 28

The regulation of plasminogen activators (PA) and their inhibitors (PAI) in the rat cell lines: HTC and L2 was studied. HTC plasminogen activator inhibitor type 1 (PAI-1) production was stimulated by dexamethasone, serum factors and insulin; that of tissue-type plasminogen activator (tPA) by cAMP raising agents. Retinoic acid, butyrate, phorbol ester and endotoxin did not affect net PA/PAI activity elaborated by HTC. L2 cells produced tPA, which production was stimulated by retinoic acid, phorbol myristate acetate, butyrate and cAMP; serum factors blunted their response, whereas in the synthetic serum substituting medium Ultraculture and with cocktail Ultroser the action of tPA stimulators was enhanced.
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PMID:Regulation of plasminogen activation in rat cell lines. 128 21

Anaphylactic shock was induced in rabbits by injecting bovine serum albumin (BSA) as an antigen. Measurements of the enzyme activities in the fibrinolytic system confirmed that a rapid and strong increase of plasminogen activator (PA) was induced during anaphylaxis. The euglobulin fibrinolytic activity (EFA) as estimated by the plasminogen-rich fibrin plate method rose significantly, peaking at 15 min after the BSA injection (when the arterial pressure was minimum). However, EFA was not detected by the plasminogen-poor fibrin plate method. The tissue-type PA (t-PA) activity using the natural substrate plasminogen increased significantly with a peak at 15 min. The amidolytic activity also simultaneously increased significantly using the t-PA substrate, H-D-Ile-Pro-Arg-pNA. The plasminogen activator inhibitor (PAI) activity remained at baseline levels until 30 min, but rose fourfold at 90 min. The main plasma fibrinolytic enzyme which increased in anaphylaxis was proved by zymography to be t-PA with a molecular weight (MW) of 69,000.
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PMID:A rapid and strong increase of plasminogen activator induced by experimental anaphylaxis in rabbits. 129 30

In thrombolytic model in vitro, reptilase (Rep, defibrase) did not show appreciable thrombolytic actions on red and white thrombi. After daily iv infusion of Rep 0.25 IU for 10 d, the time of 50% lysis of euglobulin (ELT1/2) was shortened from 9.3 +/- 0.8 to 6.7 +/- 1.0 h (P < 0.01), alteplase activity was increased from 1.9 +/- 0.7 to 3.7 +/- 0.9 IU.ml-1, and plasminogen inactivator (PI) activity reduced from 4.3 +/- 0.6 to 1.8 +/- 0.9 AU.ml-1 (all P < 0.01). The findings indicate that the thrombolytic action of Rep shown in vivo may not be from the direct action on thrombi but from the influence on alteplase and PI activity.
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PMID:Thrombolytic actions of reptilase. 130 49

A hundred and eighty three patients with a primary myocardial infarction less than 4 hours old were included in a double blind trial versus placebo comparing an isolated plasminogen streptokinase activator complex (APSAC: 30 mu in 5 mn) and tissue type plasminogen activator (rt PA: 10 mg bolus followed by 90 mg in 130 mn). Clinical evolution, side effects, patency of the artery responsible for infarction, left ventricular contractile function (contrast angiography on the 7th day and angioscintigraphy on the 21st day) and infarct size were studied. The two groups were comparable in age (54 +/- 11 years), delay in randomisation (170 +/- 50 mn), infarct site and severity of cardiac failure. There was no significant difference in hospital mortality (7 in the rt PA group and 5 in the APSAC group) or in adverse effects (haemorrhage: rt PA: 9 patients, APSAC: 11 patients). The patency was 72% in the APSAC and 76% in the rt PA group. Left ventricular function and infarct size were comparable in the two groups: angiographic EF (0.50 +/- 0.1 in the APSAC and 0.52 +/- 0.1 in the rt PA group: NS); asynergic score (11.3 +/- 1.7 in the APSAC and 10.5 +/- 1.8 in the rt PA group: NS); infarct size (10.9 +/- 8.0 in the APSAC and 9.4 +/- 7.2 in the rt PA group: NS). This trial shows that these two thrombolytic agents have the same efficacy. The authors recommend adaptation of the dosage of rt PA to body weight.
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PMID:[Study of new thrombolytic agents in myocardial infarction: a multicenter randomized trial (APSAC versus rt-PA)]. 130 Sep 57

Potential approaches to improve thrombolytic agents comprise the construction of mutants and variants of tissue-type plasminogen activator (tPA) or of single chain urokinase-type plasminogen activator (scuPA, pro-urokinase), of chimeric plasminogen activators and of conjugates of plasminogen activators with monoclonal antibodies. tPA mutants have been constructed with altered pharmacokinetic properties or altered functional properties, including binding to and stimulation by fibrin, resistance to plasmin and to protease inhibitors. Mutants of tPA described to date, obtained by deletion/substitution of functional domains or of single amino acids, have markedly reduced clearances, but usually also reduced specific thrombolytic potencies. Mutants of scuPA with improved thrombolytic potencies have thus far not been reported. Chimeric molecules containing functional domains of both tPA and scuPA have intact enzymatic properties of uPA and some fibrin affinity of tPA. Surprisingly, chimeras endowed with fibrin affinity usually have unaltered or reduced thrombolytic potencies. However, a chimera consisting of amino acids 87-274 of tPA and amino acids 138-411 of scuPA, with negligible fibrin affinity, has a 10-fold higher thrombolytic potency than scuPA in animal models of venous thrombosis, as a result of a delayed in vivo clearance and a relatively maintained specific thrombolytic activity. Plasminogen activators conjugated with antifibrin or antiplatelet monoclonal antibodies, either chemically or by recombinant DNA technology, are targeted to blood clots, resulting in a 5- to 10-fold increased thrombolytic potency. Thus, it is possible to develop plasminogen activators with improved thrombolytic potency. Whether such agents will be clinically useful remains to be established.
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PMID:Remaining perspectives of mutant and chimeric plasminogen activators. 130 56

We have generated site-specific mutants of the kringle 2 domain of tissue-type plasminogen activator [( K2tPA]) in order to identify directly the cationic center of the protein that is responsible for its interaction with the carboxyl group of important omega-amino acid effector molecules, such as epsilon-amino caproic acid (EACA). Molecular modeling of [K2tPA], docked with EACA, based on crystal structures of the kringle 2 region of prothrombin and the kringle 4 domain of human plasminogen, clearly shows that Lys33 is the only positively charged amino acid in [K2tPA] that is sufficiently proximal to the carboxyl group of the ligand to stabilize this interaction. In order to examine directly the importance of this particular amino acid residue in this interaction, we have constructed, expressed, and purified three recombinant (r) mutants of [K2tPA], viz., Lys33Thr, Lys33Leu, and Lys33Arg, and found that only the last variant retained significant ability to interact with EACA and several of its structural analogues at neutral pH. In addition, another mutated r-[K2tPA], i.e., Lys33His, interacts very weakly with omega-amino acids at neutral pH and much more strongly at lower pH values where His33 would be expected to undergo protonation. This demonstrates that any positively charged amino acid at position 33 satisfies the requirement for mediation of significant bindings to this class of molecules. Since, in other kringles, positively charged residues at amino acid sequence positions homologous to Lys68, Arg70, and Arg71 of [K2tPA] have been found to participate in kringle interactions with EACA-like compounds, we have also examined the binding of EACA, and some of its analogues, to three additional r-[K2tPA] variants, i.e., Lys68Ala, Arg70Ala, and Arg71Ala. In each case, binding of these omega-amino acids to the variant kringles was observed, with only the Lys68Ala variant showing a slightly diminished capacity for this interaction. These investigations provide clear and direct evidence that Lys33 is the principal cationic site in wild-type r-[K2tPA] that directly interacts with the carboxyl group of omega-amino acid effector molecules.
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PMID:Direct identification of lysine-33 as the principal cationic center of the omega-amino acid binding site of the recombinant kringle 2 domain of tissue-type plasminogen activator. 130 92

How heparin inhibits vascular smooth muscle cell proliferation and migration has not been established. We have investigated the hypothesis that heparin inhibits vascular smooth muscle cell proliferation and migration by interfering with the expression and activity of proteases such as plasminogen activators. In an in vitro mitogenesis model, tissue-type plasminogen activator (tPA) mRNA and protein increase in baboon smooth muscle cells stimulated with fetal bovine serum or phorbol esters. Heparin inhibits smooth muscle cell proliferation and suppresses the induction of tPA mRNA and protein while it has little effect on the mRNA of urokinase-type plasminogen activator, plasminogen activator inhibitor type I, and a number of genes that are also modulated by serum and phorbol esters. The inhibitory effect on tPA mRNA is specific to heparin-like molecules and does not depend on the anticoagulation activity of heparin. The increase in tPA mRNA is due to increased transcription, which is suppressed by heparin. The induction of tPA by serum and phorbol esters is diminished by protein kinase C inhibitors such as H7 or staurosporine and by protein kinase C depletion. Since heparin suppresses the induction of the tPA gene by phorbol esters, these results suggest that heparin may interfere with the protein kinase C pathway.
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PMID:Heparin selectively inhibits the transcription of tissue-type plasminogen activator in primate arterial smooth muscle cells during mitogenesis. 131 Jun 87


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