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)

In separate experiments, antibodies to plasminogen, factor X and protein C were applied to microtitre trays as commonly used in enzyme-linked immunoassays. After incubation with dilute normal human plasma as a source of the corresponding proenzyme antigen, the wells were exposed to dilutions of various snake venoms. After thorough washing, the microtitre tray wells were tested overnight with chromogenic tripeptide substrates known to be relatively specific for the activated forms of the above factors, i.e., plasmin, factor Xa and activated protein C. The immunochromometric assay described detected two new activators of protein C in Agkistrodon piscivorus and Agkistrodon contortrix venoms and a new factor X activator in Agkistrodon rhodostoma venom. Gel filtration of the latter venom indicated that the factor X activator eluted with high molecular weight, was clearly distinct from the peak fibrinogen clotting activity (Ancrod) and appeared to have no procoagulant activity. Although several Bothrops venoms appeared to contain plasminogen activator by this technique, the observed strong chromogenic activity was observed in microtitre wells independently of plasminogen and represented nonspecific amidase activity.
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PMID:Detection of specific proenzyme activators in snake venoms by a new immunoabsorbant-chromogenic substrate method. 384 Oct 12

Utilizing modified immunochemical methods (ELISA and radioimmunoassay) tissue plasminogen activator, B beta 15-42 RPs and protein C antigen levels were measured in man and a subhuman primate model after subcutaneous and intravenous administration of various low molecular weight heparin fractions. A wide scatter in the data was observed in the t-PA and B beta 15-42 RP levels; however, statistical analysis of the data revealed that certain low molecular weight heparin fractions increased the levels of these endogenous markers of fibrinolysis. No significant alteration in the protein C levels was noted at any time; however, a wide scatter in these data was also evident. The profibrinolytic actions of low molecular weight heparin fractions may be related to the release of t-PA, which is easily measured in plasma. Since it has strong affinity for endogenous sites (thrombus, surface), wide scatter in the data may occur. Physical exercise may also increase the levels. Most of the results reported in our studies represent data on blood samples that were obtained using the simple venipuncture method. We also find that the intravenous administration of the low molecular weight heparin fractions also caused a shortening of the ELT. Since the low molecular weight heparin fractions are heterogeneous in nature, the profibrinolytic actions may be related to one or more of these constituent fragments. Thus, the molecular identity of the profibrinolytic component of low molecular weight fractions remains unknown at this time. Also unknown is if there is a relationship between this effect and anticoagulant activity.
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PMID:Studies on the profibrinolytic actions of heparin and its fractions. 387 99

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator-inhibitor. High concentrations of thrombin-but not of factor Xa or IXa--had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.
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PMID:Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. 391 96

Fibrinolysis may be impaired in coronary heart disease patients. 20 coronary heart disease patients and 10 control subjects were examined for tissue-plasminogen activator activity, tissue-plasminogen activator antigen, fast tissue-plasminogen activator inhibitor and other fibrinolytic and haemostatic parameters including antigenic and functional protein C. Both patient and control groups were similar in age and smoking habits. All of these patients had a myocardial infarction between 1-3 months before this study. Assays were evaluated before and after an exercise test. Prothrombin time, activated partial thromboplastin time, protein C, plasminogen, alpha 2-antiplasmin, fibrinogen/fibrin degradation products and contact-activated fibrinolysis were similar before and after exercise in both groups. Fibrinolytic activity assayed by the euglobulin lysis time and fibrin-plate lysis methods was decreased in the patient group as compared with the control group but the difference was not significant. In basal conditions, tissue-plasminogen activator activity was defective in 50% of the coronary heart disease patients (p less than 0.01) and after exercise this percentage rose to 77% (p less than 0.01). However, tissue-plasminogen activator antigen in the coronary heart disease group was similar to that of the control group, both before and after exercise. The activity of the tissue-plasminogen activator inhibitor was persistently increased in coronary heart disease though this increase was not statistically significant. It is concluded that in coronary heart disease patients there is a defective fibrinolytic activity probably due to an increase in tissue-plasminogen activator inhibitor.
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PMID:Reduced fibrinolytic activity in coronary heart disease in basal conditions and after exercise. 408 14

Activated protein C is a vitamin K-dependent plasma protein which inhibits blood coagulation at the levels of factors V and VIII in the clotting cascade and which enhances blood clot lysis by raising the levels of circulating plasminogen activator. Activation of protein C occurs when thrombin binds to an endothelial cell associated cofactor, thrombomodulin. The thrombin-thrombomodulin complex rapidly activates the protein C. The activated protein C has a relatively long half-life in plasma and thus can serve as a circulating anticoagulant as well as elevate the levels of plasminogen activator. Heparin interacts with the protein C system in at least two distinct ways. First, the activation of protein C in vivo can be blocked by administration of low levels of heparin. The heparin brings about the inhibition of thrombin either before thrombin is bound to the cell-associated thrombomodulin or after the thrombin is complexed to the thrombomodulin. Secondly, activated protein C has its own unique inhibitor, activated protein C inhibitor. Inhibition of activated protein C by this inhibitor is stimulated by relatively high levels of heparin (5-10 u/ml). The physiologic significance of heparin-activated protein C inhibitor remains to be demonstrated.
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PMID:Heparin-protein C interaction. 608 2

An endothelial cell-associated cofactor that greatly enhances the rate of protein C activation by thrombin has recently been described. The observation that the cofactor binds thrombin with unusually high affinity (K(d) = 0.5 nM) suggested that low level thrombin infusion into dogs might lead to the selective activation of protein C. Infusion of thrombin (1 U/min per kg body wt) into the jugular vein of dogs leads to the formation of a systemic anticoagulant activity within 5 min of starting the infusion. The plasma has a prolonged partial thromboplastin time and Factor X(a) clotting time, but there is no change in the thrombin clotting time. The systemic anticoagulant activity is identified as activated protein C for the following reasons: (a) anti-canine activated protein C IgG antibodies inhibit the anticoagulant activity; (b) the anticoagulant activity can be partially purified from the plasma of dogs infused with thrombin by barium citrate adsorption; (c) the anticoagulant has chromatographic properties on QAE Sephadex indistinguishable from those of activated protein C, and (d) the rate at which this anticoagulant is inhibited in citrated canine plasma is identical to that of canine activated protein C. The in vivo activation of protein C appears to be receptor mediated since it occurs at low thrombin concentration and since it can be progressively inhibited by simultaneous infusion of diisopropylphospho-thrombin with thrombin. The activation of protein C at low levels of thrombin is selective, since neither the platelet count nor the Factor V levels are altered. Thrombin infusion leads to an elevation in circulating plasminogen activator levels. This appears to be mediated through the activation of protein C since coinfusion of diisopropylphospho-thrombin with thrombin inhibits the increase in plasminogen activator levels. Pretreatment of dogs with dicumarol blocks both the formation of anticoagulant activity and the rise in plasminogen activator. When the dicumarol-treated dogs are supplemented with isolated protein C and thrombin is infused, the anticoagulant activity again appears and the circulating levels of plasminogen activator are again elevated. These studies illustrate that low levels of thrombin in vivo can activate protein C, which in turn can inhibit blood coagulation and initiate fibrinolysis by elevating circulating plasminogen activator levels.
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PMID:Activation of protein C in vivo. 617 16

The effect of orally-administered stanozolol, 5 mg b.d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and antithrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects. The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, "free" plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.
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PMID:Stanozolol-induced changes in fibrinolysis and coagulation in healthy adults. 674 May 47

The role of the microvascular endothelium in the integration of inhibitory and catabolic pathways of hemostasis is discussed in light of recent findings of direct biochemical links between endothelium and regulatory plasma proteins. These findings include the following: (1) On the vascular endothelium, a cofactor for antithrombin III (with an activity comparable to stationary phase heparin) catalyzes thrombin inhibition in vivo. (2) A second cofactor on endothelium binds thrombin in a manner that enhances by several orders of magnitude the ability of thrombin to activate protein C. (3) Activated protein C has both anticoagulant and catabolic activities; anticoagulant activity results from the susceptibility of factors Va and VIIIa to inactivation by activated protein C, whereas catabolic activity arises from the stimulation by activated protein C of the release from endothelium of fibrin-dependent plasminogen activator. (4) Because it requires fibrin as a cofactor, the plasminogen activator lyses clots without provoking fibrinogenolysis. Location of these activities on endothelium separates coagulation in time and space from catabolic pathways, and provides for their expression after the initiation of hemostasis.
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PMID:The control of hemostasis. Role of endothelium in the regulation of inhibitory and catabolic pathways. 689 31

The ECAT Angina Pectoris Study is a European multicentre study with the aim of investigating the pathogenetic and predictive role of haemostatic factors in the progression of coronary heart disease. It is the largest study performed up to now with regard to both the number of patients with angina pectoris (n = 3043) and the number of haemostasis assays (n = 23) included. The present paper presents baseline cross-sectional data with particular reference to the relationship of haemostatic factors with each other and with the coronary risk factors age, gender and acute-phase reaction (1). Two clusters of haemostatic factors could be distinguished in which each variable was correlated (P < 0.001) to every other variable: (a) Eight fibrinolysis assays including t-PA, PAI-1 and euglobulin clot lysis time (ECLT), for which PAI-1 appeared to be the dominating factor; (b) antithrombin III, protein C, alpha 2-antiplasmin and plasminogen, the interdependence of which has no obvious explanation. (2). Twelve out of the 23 haemostasis assays were associated (P < or = 0.01) with age. Except for alpha 2-antiplasmin, these relationships indicated an increased tendency to thrombosis with increasing age. (3). Gender differences found in 14 haemostasis parameters do not indicate a consistent difference in the tendency to thrombosis between men and women. Eight haemostasis parameters were on average higher in female than in male patients in the age group over 50 years. (4). C-reactive protein, an acute-phase reactant, was positively correlated (P < 0.001) with fibrinogen, factor VIIIc, von Willebrand factor, the fibrinolysis assays t-PA, PAI-1, ECLT and plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemostasis factors in angina pectoris; relation to gender, age and acute-phase reaction. Results of the ECAT Angina Pectoris Study Group. 749 59

Activated protein C (APC)-protein C inhibitor (PCI) complex level was examined in 35 patients with acute pulmonary embolism (PE) and in 20 healthy volunteers. Thrombin-antithrombin III complex, plasmin alpha 2 plasmin inhibitor complex, and fibrin-D-dimer levels were significantly increased in the patients with PE compared to levels in healthy volunteers. Levels of plasminogen activator inhibitor-I, tissue type plasminogen activator, and von Willebrand factor antigens were also significantly increased in patients with PE. Plasma level of APC-PCI complex was increased in most patients with PE and APC-alpha 1 antitrypsin complex level was increased in 13 patients. These complexes were not detected in healthy volunteers. These findings suggested that plasma protein C was activated in patients with PE, and that PCI was the major inhibitor of APC generated in this condition. Thus, regulation of the protein C pathway might play an important role in the pathogenesis of PE.
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PMID:Increased activated protein C-protein C inhibitor complex levels in patients with pulmonary embolism. 751 16


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