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

---

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

Results of blood coagulation and hematologic studies on 6 goats, each tested 3 times, were compared to the values seen in persons. Special blood platelet studies were done on an additional goat. Blood coagulation values in the goats and in persons were similar, with these exceptions: In the goat, activated partial thromboplastin time was shorter and thrombin time was longer; one-stage assays of factors V, VIII, and IX were very high, and platelets aggregated poorly epinephrine and ristocetin. Both platelets and erythrocytes were small. On scanning electron microscopy, the erythrocytes appeared as flat disks or triangles, occasionally having a dimpled center, compared to the deeply dimpled doughnut shape of the larger human erythrocytes. Osmotic fragility of these small erythrocytes was greater than that of their human counterparts. By transmission electron microscopy of ultrathin sections of goat buffy coat, platelets had fine structures similar to those of human platelets. Unlike in human platelets, most of the dense bodies in goat platelets were surrounded by clear vacuoles. Biochemical studies showed higher than human levels of phosphorus, chloride, sodium, alkaline phosphatase, and serum glutamic oxaloacetic transaminase.
...
PMID:Comparative hematology: studies on goats. 127 47

This study contrasts the protein composition of the detergent-resistant cytoskeleton of platelets fully spread on glass with the cytoskeletal composition of resting platelets and platelets aggregated in suspension with thrombin. Complete Triton X-100-insoluble cytoskeletons were isolated from spread, resting, and suspension-activated platelets in the presence of protease inhibitors, solubilized in sodium dodecyl sulfate/EDTA and analyzed on reduced, one-dimensional polyacrylamide gels. The protein composition of the cytoskeletons differed both qualitatively and quantitatively. Most notable were more extensive incorporation of total protein, talin, and vinculin into the cytoskeleton of spread platelets than the cytoskeleton of suspension-activated platelets. Varying the concentration and time of exposure to thrombin during suspension activation did not mimic the cytoskeletal changes of surface activation. Scanning electron microscopy, measurement of lipid phosphorus content, and varying the duration of Triton extraction did not show incomplete solubilization or nonspecific trapping of constituents in the spread platelet cytoskeleton. Proteolysis of talin was minimal in suspension-activated platelets and in platelets spread for 50 minutes. The differences in the detergent-resistant cytoskeletons of surface- and suspension-activated platelets indicate significant divergence in the physiologies of platelet spreading on surfaces and platelet activation in suspension.
...
PMID:Detergent-resistant cytoskeleton of the surface-activated platelet differs from the suspension-activated platelet cytoskeleton. 145 Apr 4

We previously have described the ability of alpha-thrombin (the native procoagulant enzyme) to stimulate adherence of neutrophils to pulmonary artery endothelial cells. In the present study, we observed that conditioned medium factors released by alpha-thrombin (10(-8) M) treatment of cultured ovine pulmonary artery endothelial cells increased neutrophil adherence to naive pulmonary artery endothelial monolayers. This effect was independent of any residual alpha-thrombin present in the medium. In contrast to thrombin-induced neutrophil adherence, adherence of neutrophils mediated by the conditioned medium was not inhibited by the anti-CD18 monoclonal antibody 60.3, indicating a CD18-independent mechanism. The factors generated by the action of alpha-thrombin on endothelial cells also resulted in concentration-dependent neutrophil migration. The neutrophil adherence- and migration-promoting activities were isolated in the ether portion after extraction of the conditioned medium. Chromatographic analysis showed that the active components (which resolved into two peaks by reversed-phase high-performance liquid chromatography) were relatively hydrophilic low molecular weight lipids without phosphorus or amino acids. Reconstitution of these peaks indicated that they mediated neutrophil adhesion and migration responses. The results indicate that lipid factors promoting neutrophil adhesion and migration are generated by the action of thrombin on pulmonary artery endothelial cells. The generation of these factors may contribute to the amplification of the lung inflammatory response after pulmonary intravascular coagulation induced by thrombin.
...
PMID:Thrombin-mediated release of lipids from pulmonary artery endothelial cells promotes neutrophil adherence. 167 31

In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with 32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05-0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Platelet phospholipase C activity in salt-dependent hypertension. 231 20

Individuals with diabetes mellitus may have increased in vivo platelet activity. Abnormal platelet function could contribute to the increased incidence of vascular disease in diabetes mellitus. The biochemical mechanism(s) for platelet hyperactivation is unknown. We examined the hypothesis that platelet phosphoinositide turnover, a key signal-transducing mechanism involved in platelet activation, was abnormal in diabetic subjects. Platelets were harvested from 16 subjects with insulin-dependent diabetes mellitus (IDDM) and 19 healthy, nondiabetic control subjects of comparable age. Plasma beta-thromboglobulin (beta-TBG), a specific marker of platelet activity in vivo, was increased in IDDM (67.1 +/- 7.3 ng/ml) compared with control (41.0 +/- 6.0 ng/ml) subjects (P less than .005). [32P]orthophosphate (32Pi) incorporation into the individual phosphoinositides and phosphatidic acid (PA) reached isotopic equilibrium by 120 min for IDDM and control subjects. Specific activity (dpm 32P/micrograms phosphorus) of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was not different between IDDM and control subjects. Under these conditions, basal 32Pi incorporation into PIP2 and PIP but not phosphatidylinositol (PI) or PA was significantly lower in IDDM subjects. There was significantly decreased [32P]PIP2 and [32P]PIP hydrolysis and decreased [32P]PA formation in IDDM after platelet stimulation with 4 U/ml human thrombin. There were no differences in [32P]PI hydrolysis between the two groups. The mass of PIP2 was reduced (P less than .005) in the platelets from IDDM (0.71 +/- 0.23 nmol/10(9) platelets) compared with control (1.65 +/- 0.53 nmol/10(9) platelets) subjects. Similarly, PIP was lower (P less than .001) in IDDM (0.66 +/- 0.09 nmol/10(9) platelets) than in control (2.92 +/- 0.43 nmol/10(9) platelets) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Decreased platelet phosphoinositide turnover and enhanced platelet activation in IDDM. 254 8

Plasmalogen lysophosphatidylethanolamine (LPE) in rabbit platelets was quantitatively determined as glycero-3-phosphorylethanolamine (GPE) after treatment with 5% trichloroacetic acid at 20 degrees C for two hours. GPE was measured directly using a high performance liquid chromatography with monitoring the fluorescence of o-phthaldialdehyde/2-mercaptoethanol adducts. The assay was sensitive to 50 pmol of plasmalogen LPE and was linear over a 200-fold concentration range. While, 1-acyl LPE and phosphatidylethanolamine from bovine brain (containing about 50% plasmalogen) were hardly cleaved to GPE under the same conditions. These procedures were specific for plasmalogen LPE, and simpler and more sensitive in comparison with conventional analytical methods, e.g., two-dimensional thin layer chromatography with subsequent phosphorus assay. Employing the present method, plasmalogen LPE was found to increase rapidly and to decrease subsequently when rabbit platelets were stimulated by thrombin.
...
PMID:A simple and sensitive determination for plasmalogen lysophosphatidylethanolamine in rabbit platelets. 281 36

Experiments to explore human platelet protein phosphorylation changes and 5-hydroxytryptamine (5-HT) secretion after challenge with cotton bract tannin were performed. Quantitative changes in sodium phosphate phosphorus 32 incorporation in two platelet proteins of 19 kilodaltons (kd) and 47 kd were assessed by measuring protein band densities on autoradiographs of dried polyacrylamide gels. Secretion of 5-HT was assessed by 14C-5-HT release. Results show that tannin causes increases in phosphorylation of discrete platelet proteins that begin in less than 2 seconds. These increases are maximal in 1 minute for the 47 kd protein and in 3 minutes for the 19 kd protein. Fifty percent of maximum response required less than 2 seconds for both of these proteins, and 50% of maximum 5-HT secretion required 48 seconds. Dose-response studies comparing 0 to 50 micrograms/ml tannin with 0 to 1 U/ml human alpha-thrombin showed that tannin caused 5-HT secretion and protein phosphorylation changes that were very similar to those induced by human alpha-thrombin. Fifty micrograms per milliliter of tannin caused increases in 19 kd protein phosphorylation and 47 kd protein phosphorylation to 312% +/- 34% (SEM) and 204% +/- 13% of control, respectively (n = 14). One unit per milliliter of thrombin induced changes of 350% +/- 40% and 221% +/- 17% of control in the 19 kd and 47 kd proteins, respectively. Release of 5-HT by tannin and thrombin was 61% +/- 3% and 69% +/- 3% of total cellular 5-HT, respectively. Indomethacin had little inhibitory effect on activation by these two different agents.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Protein phosphorylation during tannin-mediated activation of human platelets. 334 45

The synthesis of the tripeptide D-Phe-Pro-Arg with the nitrile group instead of the carboxylgroup is described. Initially, the corresponding peptide amide was synthesized by conventional methods in solution using Boc and Fmoc as the protecting group for D-Phe. The dehydration in order to create the nitrile moiety was achieved by treating the peptide amide with phosphorus oxichloride or trifluoroacetic anhydride. Best results were obtained by the use of phosphorus oxichloride in pyridine as the solvent in the presence of imidazole. After deprotection of the N-terminal amino acid the crude product was purified by chromatography on Butyl-Fractogel HW-40 (S). The purity of the final product was checked on a RP18 phase by hplc. The existence of the nitrile group was demonstrated by i.r. and 13C-n.m.r. spectra. The peptide nitrile exhibited a strong inhibition of thrombin compared to the tripeptide amide.
...
PMID:Synthesis of a tripeptide with a C-terminal nitrile moiety and the inhibition of proteinases. 336 43

1. Fibrin clots obtained from diluted human plasma with bovine thrombin often contain amounts of phospholipids that cannot be diminished by further plasma dilution. 2. The ;cold insoluble residue' obtained during fibrinogen preparation has a higher phosphorus content than the purified fibrinogen. 3. Evidence showed that adsorption of phospholipids or phosphorus-containing fibrinopeptides on purified fibrinogen or fibrin was unlikely. 4. O-Phosphorylserine was detected in acid hydrolysates of human fibrin. 5. On the basis of phosphorus determinations the average molecular weight of human fibrinogen cannot be less than 342000 (304000-383000) for a group of ten donors, and 265000 for two other persons, assuming 1 phosphorus atom/molecule and incomplete splitting of the phosphorus-containing fibrinopeptide. Complete splitting of the phosphopeptide would require molecular weights twice as high. 6. Fibrinolysis was a possible cause of lower phosphorus contents found in isolated fibrinogen and fibrin from a donor who showed apprehension during blood collection and in a fibrinogen preparation that had been submitted to prolonged dialysis.
...
PMID:Molecular weight of human fibrinogen derived from phosphorus determinations. 586 26

The addition of thrombin to horse platelets prelabeled with 32P induces a rapid decrease of the radioactivity from phosphatidylinositol 4,5-bisphosphate. Maximum loss of the radioactivity from phosphatidylinositol 4,5-bisphosphate occurs with 10 s of stimulation and is followed by an increased incorporation of 32P into this lipid. The stimulation of phosphatidylinositol 4,5-bisphosphate loss by thrombin is concentration-dependent. The ionophore A23187, which mobilizes Ca2+, is ineffective in inducing the degradation of phosphatidylinositol 4,5-bisphosphate. Measurements of polyphosphoinositides by phosphorus estimation show that, 10 s after thrombin stimulation, there is a decrease of 15-20% of the total phosphatidylinositol 4,5-bisphosphate without any significant change in phosphatidylinositol 4-monophosphate. It appears that thrombin causes a rapid and transient degradation of phosphatidylinositol 4,5-bisphosphate and that this effect might be related to the initiation of platelet activation.
...
PMID:Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets. 629 Apr 78


1 2 3 4 Next >>

---