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: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ultrastructure, cytochemistry, biochemistry, and functions of platelets from two patients with the familial gray platelet syndrome are described. Ultrastructural studies showed a lack of alpha-granules in the megakaryocytes in the vicinity of a marrow myelofibrosis and/or in platelets. A normal number of mitochondria and a slight increase of dense bodies was confirmed by labeling the whole patient with mepacrine. Platelet peroxidase (in the dense tubular system) and catalase-positive granules (revealed by the cytochemistry) were present. Platelets from both patients had severe deficiency of beta TG either after tritonization (less than 4% of normal) or thrombin treatment (less than 15% of normal), and the plasma beta TG levels were slightly increased. Functional studies of these platelets showed an uptake of [14C]5HT inhibited by reserpine similar to that in the control platelets. Thromboxane formation was within normal limits in the presence of arachidonic acid, ADP, collagen, or ionophore A23187, indicating that (1) the cyclooxygenase/thromboxane synthetase systems were not altered and (2) the phospholipase activities were not impaired. Although the platelet adhesion to prepolymerized fibrillar type III collagen and the ADP-, arachidonic acid-, and ionophore A23187-mediated aggregations were apparently normal, in every case the release of [14C]5HT was either at the low side of the normal range or decreased. This abnormality was increased when collagen or thrombin was added to either PRP or washed platelets from both patients, where at the same time, the aggregation and the release were markedly reduced. The results suggest that alpha-granules or their content has an influence on not only the platelet aggregation but also the dense bodies involved in the [14C]5HT release reaction.
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PMID:Gray platelet syndrome: alpha-granule deficiency. Its influence on platelet function. 645 43

Advances in biochemistry, physiology, immunology, and cytochemistry, combined with a variety of new approaches for the evaluation of fine structure, have yielded new insights into the structural physiology and pathology of blood platelets. Subpopulations of platelet granules have been clearly defined; they include the catalase containing organelles referred to as peroxisomes; lysosomes enclosing hydrolytic enzymes; and the alpha-granules in which platelet factor 4, mitogenic factor, beta thromboglobulin, thrombin sensitive protein, fibrinogen, and coagulation factor V are localized. Features of platelet membrane systems have been particularly well-delineated, and recent evidence suggests that membrane complexes serve as the sarcoplasmic reticulum of platelets and the site of prostaglandin synthesis. Improved understanding of platelet biostructure resulting from these observations has made it possible to develop specific relationships between defects in structure and pathological behavior of the cells in vitro and in vivo.
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PMID:Overview article: biostructure of blood platelets. 676

The enzymes (uricase (EC 1.7.3.3), allantoinase (EC 3.5.3.4), and allantoicase (EC 3.5.2.5) which participate in degradation of purine bases, were embedded separately in fibrin membranes formed by fibrinogen-fibrin conversion with thrombin. All of these enzymes together with catalase were also embedded in a single fibrin membrane to make an immobilized multienzyme complex. The multienzyme complex in fibrin membrane thus prepared had an ability of degradation of uric acid to urea and glyoxylic acid via allantoin and allantoic acid. The stability of immobilized uricase or catalase embedded in fibrin membrane upon lyophilization was also tested in a comparison with nonimmobilized enzymes.
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PMID:Fibrin membrane endowed with biological function. V. Multienzyme complex of uricase, catalase, allantoinase and allantoicase. 698 99

Previous studies have established that cigarette smoking results in acute platelet hyperaggregability. We investigated whether changes in plasma oxidative properties could occur after smoking and whether such changes could be responsible for this enhanced platelet activity. In the present work, we report that platelets from nonsmokers become hyperactive after incubation with plasma prepared from blood of smokers obtained 10 min after smoking. This effect was not observed with presmoking plasma and could be inhibited in vitro by adding either catalase or reduced glutathione plus peroxidase to plasma or 2,6-di-tert-butyl-p-cresol (BHT) to platelets before incubation. Comparison of pre- and postsmoking plasma showed that smoking resulted in a decrease in vitamin E (18%, P < 0.01) and increases in conjugated diene (35%, P < 0.001), thiobarbituric acid-reactive substance (23%, P < 0.02), and free fatty acid (FFA, 40%, P < 0.005) plasma concentrations. The FFA fraction was peroxidized to a higher extent when extracted from postsmoking than from presmoking plasma. This peroxidized FFA fraction enhanced the thrombin-induced aggregation of platelets from nonsmokers. This increased response was inhibited either when the peroxidized FFA fractions were isolated from plasma treated with reduced glutathione and peroxidase or by pretreatment of the platelets with BHT. We conclude that the enhanced formation of lipid hydroperoxides found in postsmoking plasma seems to be responsible for the acute and marked platelet hyperactivity observed after smoking.
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PMID:Involvement of hydrogen and lipid peroxides in acute tobacco smoking-induced platelet hyperactivity. 786 94

Venoms of several snake species contain large amounts of L-amino acid oxidase but its effects on human plasma coagulation and platelet aggregation have not been explored. We have purified L-amino acid oxidase from king cobra venom through CM-Sephadex C-25, Sephadex G-100 and DEAE Sephadex A-50 chromatographies. The purified enzyme has a mol. wt of 135,000 as determined by gel filtration and 65,000 by SDS-PAGE under non-reducing and reducing conditions. Incubation of plasma with L-amino acid oxidase at 200 micrograms/ml did not affect prothrombin time, activated partial thromboplastin time, or thrombin time. Upon addition of L-amino acid oxidase, platelets in platelet-rich plasma were aggregated. The enzyme-induced aggregation was abolished by catalase. The aggregation was also inhibited by indomethacin, aspirin, ethylenediaminetetraacetate, sodium nitroprusside, prostaglandin E1, mepacrine and verapamil, but not by heparin, hirudin, creatine phosphate/creatine phosphokinase or antimycin/2-deoxy-D-glucose. These results suggest that L-amino acid oxidase induces human platelet aggregation through the formation of H2O2, and subsequent thromboxane A2 synthesis requiring Ca2+ but independent of ADP release. The platelet aggregation caused by L-amino acid oxidase is likely to contribute to toxicity inflicted by cobra venom.
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PMID:Purification and characterization of L-amino acid oxidase from king cobra (Ophiophagus hannah) venom and its effects on human platelet aggregation. 788 93

Endogenous nitric oxide (NO, endothelium-derived relaxing factor) was stimulatory for histamine- and suppressive for serotonin-induced paw edema of mice. This action was mediated by guanosine 3',5'-cyclic monophosphate production. Local injection of superoxide dismutase (SOD), catalase, NG-monomethyl-L-arginine (L-NMMA), methylene blue and Desferal (iron chelator) mixed with mediator suppressed histamine-induced edema at doses between 0.1 and 100 micrograms/kg and showed no or little stimulatory effect at higher doses. L-arginine reversed the effect of L-NMMA. Serotonin edema was enhanced by a high dose of these drugs. Their effect became suppressive as the histamine ratio was increased in edema induced by a histamine-serotonin mixture. This suggested that serotonin-induced vascular permeability decreased with a greater production of either O2- or NO. Cimetidine (H2-antagonist) was not effective in histamine edema of normal mice, but became suppressive (ED50 = 70 micrograms/kg) when 10 mg/kg L-NMMA was coinjected. SOD and methylene blue also rendered this edema sensitive to cimetidine. A simultaneous decrease in sensitivity to mepyramine (H1-antagonist) indicated that NO and oxyradicals kept H1-receptors activated. L-NMMA had no effect on bradykinin edema, but suppressed thrombin-, acetylcholine-, platelet-activating factor-, substance P- and FeCl3-induced paw edemata. Nitroprusside (NO donator) suppressed serotonin edema. N-Acetylcysteine and cytochrome c, but not ascorbate and hydroxyl radical scavengers suppressed histamine edema.
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PMID:Opposite effect of superoxide dismutase, L-arginine analogues, methylene blue and desferal: suppression of histamine-induced and stimulation of serotonin-induced paw edema in mice. 835 90

In 41 patients with coronary heart disease (CHD) the concentrations of total blood platelet malonyldialdehyde (MDA: 2.11 +/- 0.25 nmol/10(9) platelets) and MDA corresponding to thromboxane A2 (TXA2 0.84 +/- 0.13 nmol/10(9) platelets) were increased in comparison with values in blood platelets of healthy subjects (1.19 +/- 0.09 and 0.71 +/- 0.05 nmol/10(9) platelets), respectively. The increased aggregability with ADP and thrombin of patient platelets was also observed. In relation to the blood platelets of healthy subjects, the antioxidant enzymes activities of patient blood platelets were significantly (P < 0.001) decreased. Platelet glutathione peroxidase (GSH-Px) activity of the patients (11.3 +/- 0.85 U/g protein) was significantly lower than controls (18.3 +/- 1.12 U/g protein). In patients with CHD the activities of the other antioxidative platelet enzymes: catalase (Cat, 7.37 +/- 1.38 U/g protein) and superoxide dismutase (SOD, 1529.4 +/- 167 U/g protein) were also significantly decreased in comparison with values for healthy subjects (Cat: 9.06 +/- 1.30 U/g protein and SOD: 1987 +/- 230 U/g protein, respectively). It is suggested that antioxidative defense in blood platelets may affect the haemostatic processes and lipid peroxidation in patients with CHD.
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PMID:Changes in antioxidant enzymes activities, aggregability and malonyldialdehyde concentration in blood platelets from patients with coronary heart disease. 835 54

Fibrin thrombi form at sites of injury, where leukocytes release a variety of oxidants. To determine whether oxidants might affect proteins of the fibrinolytic system, we examined the effects of various oxidants on plasmin. Plasmin was not inhibited by micromolar concentrations of hypochlorous acid, chloramine T, or H2O2. Neither Fe nor Cu affected plasmin alone or in the presence of H2O2. However, incubation of plasmin with 5 mumol/L Cu(I or II) in the presence of the reducing agent ascorbic acid resulted in a loss of its hydrolytic activity towards proteins as well as towards small synthetic substrates. The addition of EDTA, but not mannitol, prevented its inactivation. Inactivation was prevented by the addition of catalase and accelerated by hydrogen peroxide. Preincubation of plasmin with the competitive inhibitor alpha-N-acetyl-L-lysine methyl ester prevented inactivation by Cu(II) and ascorbate. These results together suggest site-specific oxidation of plasmin's active site. Treatment of the plasminogen activators tissue plasminogen activator and two-chain urokinase-type plasminogen activator, as well as trypsin, neutrophil elastase, and thrombin with Cu(II) and ascorbate resulted in a loss of their amidolytic and proteolytic activity, indicating the general susceptibility of serine proteases to this type of oxidation. Oxidation of the zymogens Glu-plasminogen and single-chain urokinase-type plasminogen activator by Cu(II) and ascorbate resulted in the failure of these molecules to generate active enzymes when treated with plasminogen activators or plasmin, respectively. The active site His residue may be the target of oxidative inactivation, as evidenced by the partial protection afforded plasmin by the addition of Zn(II), histidine, or the platinum derivative, platinum(II) (2,2':6',2"-terpyridine) chloride. Because platelets contain micromolar concentrations of Cu and leukocytes are rich in ascorbate, Cu-dependent site-specific oxidation might play a role in modulating proteolytic events and the life span of thrombi formed at sites of tissue injury.
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PMID:Oxidative inactivation of plasmin and other serine proteases by copper and ascorbate. 836 3

Platelets and coagulation are involved in the pathogenesis of blood-borne metastases. The aim of this study is to obtain more information about the mechanisms involved in the initial adhesion of tumor cells to endothelial cells. In short term experiments with tumor cells, suspended in the medium of cultured endothelial cells, we tested whether addition of both platelets and thrombin cause more tumor cell adhesion to endothelial cells, than when either platelets or thrombin are acting alone. HeLa cells or HT29 cells, prelabeled with radioactive 51Cr, human platelets, and thrombin were added to human endothelial cell cultures. Following 15 min of shaking at 37 degrees C, the percentage of tumor cell adhesion was calculated. The percentages of adhering tumor cells with the presence of both platelets and thrombin were greatly increased compared to controls. Addition of hirudin 2 min before thrombin lowered the adhesion percentage of tumor cells. Hirudin added immediately before and 2 min after thrombin gave only minor effects. When the endothelium was treated with superoxide dismutase, catalase, and mannitol, the adhesion of tumor cells was lowered with catalase and superoxide dismutase. The cause of tumor cell-endothelial cell interaction is probably complex. Our results show that activated platelets enhance the tumor cell adhesion, and that generation of active oxygen species may be important in the initial phase of the interaction.
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PMID:Addition of both platelets and thrombin in combination accelerates tumor cells to adhere to endothelial cells in vitro. 911 26

In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.
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PMID:Hydrogen peroxide is involved in collagen-induced platelet activation. 942 1


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