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)

This study was designed to examine how protein kinase C (PKC) regulates the release of endothelin-1 (ET-1) from cultured porcine aortic endothelial cells. We measured the release of immunoreactive (IR)-ET-1 from cells cultured for up to 72 h in the presence or absence of a phorbol ester TPA. The release of IR-ET-1 from control cells (no TPA) increased according to time for up to 72 h. In the presence of TPA, the release of IR-ET-1 from the cells was higher than the control level for up to 8 h, but was lower thereafter and reached a plateau after 48 h. TPA dose-dependently stimulated IR-ET-1 release during incubation for 4 h, but suppressed it after incubation for 72 h. Stimulation of PKC by diacylglycerol mimicked the early (4 h) action of TPA. On the other hand, pretreatment of cells with TPA to downregulate PKC significantly suppressed basal and thrombin- or FCS-stimulated IR-ET-1 release. These findings suggest that the activation of PKC is related to the stimulation of ET-1 release and that down-regulation of PKC leads to the suppression of ET-1 release from cultured endothelial cells.
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PMID:Effect of a phorbol ester on immunoreactive endothelin-1 release from cultured porcine aortic endothelial cells. 144 49

We investigated the intracellular processes of the shape change in human megakaryoblastic leukemic cells, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by phorbol 12-myristate 13 acetate (TPA) and weakly by Ca2+ ionophore, A23187, but not by ADP, collagen, or epinephrine. Electron microscopy and FITC-labeled phalloidin staining revealed thick submembranous microfilament bundles in the pseudopods of the shape-changed cells by thrombin. Shape change was inhibited by cytochalasin B. Since Ca(2+)-dependent phosphorylation reactions play central role on the initiation of shape change of platelet, we examined the effects of protein kinase C (PKC) inhibitor, H-7, and myosin light chain (MLC) kinase inhibitor, ML-9, on the shape change of MEG-01 cells induced by thrombin, and observed that H-7 potently inhibited thrombin-induced shape change, while ML-9 did not. These results suggest that thrombin-induced reorganization of microfilaments and shape change of MEG-01 cells are mediated by PKC, but not by MLC kinase.
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PMID:Thrombin-induced shape change in human megakaryoblastic leukemic cells, MEG-01, is mediated by protein kinase C. 144

Platelet intracellular free calcium concentration [Ca2+]i from patients with essential hypertension has been found to be elevated, but the intracellular effects of this increase are still unclear. As protein phosphorylation is an important regulatory step in cell activation and increased protein phosphorylation has been demonstrated in platelets from hypertensive animals, we investigated protein phosphorylation and [Ca2+]i in platelets from patients with essential hypertension and age-matched normotensives. We measured the 32P incorporation into a 20 kDa protein and a 47 kDa protein in 17 hypertensive patients and 20 normotensive, age-matched subjects. The [Ca2+]i was measured with the fluorescent dye fura-2. Protein phosphorylation and [Ca2+]i were assessed in unstimulated platelets and after exposure of the cells to 0.1 and 0.25 U/mL thrombin at 20, 60, and 300 sec. In addition we assessed the activity of protein kinase C by incubating the platelets with phorbol-ester TPA at 20, 60, and 300 sec. Basal phosphorylation of the two proteins was not different between the two groups. After exposure of the platelets to thrombin 32P, incorporation into the 20 kDa protein and the 47 kDa protein was significantly increased in platelets from hypertensive patients at all times. Furthermore, the specific stimulation of protein kinase C with TPA resulted in a significantly higher phosphorylation of the 47 kDa protein, whereas the 20 kDa protein was not phosphorylated after incubation with TPA for 1 min. Basal [Ca2+]i was higher in platelets from hypertensive patients (124 +/- 7 nmol/L v 104 +/- 5 nmol/L, P less than .05), although there was a wide overlap between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein phosphorylation and intracellular free calcium in platelets of patients with essential hypertension. 157 40

We investigated the intracellular processes of the shape change in the human megakaryoblastic leukemia cell, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by TPA and A23187, but not by ADP, collagen, or epinephrine. Electron microscopy and FITC-labeled phalloidin staining revealed thick submembranous microfilament bundles in the pseudopods of the shape-changed cells induced by thrombin. Shape change was inhibited by cytochalasin B. Protein kinase C (RKC) inhibitor, H-7, markedly inhibited thrombin-induced shape change, while the myosin light chain kinase (MLCK) inhibitor, ML-9 did not. These results suggest that thrombin-induced reorganization of microfilaments and shape change of MEG-01 cells are mediated by PKC but not by MLCK.
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PMID:[Shape change in human megakaryoblastic leukemia cells, MEG-01]. 161 74

To clarify the relationships between free calcium levels, ATP release and aggregation potencies of SHRSP platelets, we examined the platelets from 9-month-old SHRSP and WKY using fura-2AM and luciferine-luciferase. In the absence of extracellular Ca2+, each reagent elevated the free calcium level to the same extent in the samples of both SHRSP and WKY. With regard to ATP release, thrombin and collagen less potentiated the platelet action in SHRSP than WKY, and ATP release was not affected by extracellular Ca2+. Collagen and ADP induced aggregations showed lower activities in SHRSP than WKY. TPA caused higher Ca2+ influx and aggregation activity in SHRSP than WKY in the presence of extracellular Ca2+. These results indicate that Ca2+ release must be followed by ATP release, and ATP release may be less potentiated, while thrombin and TPA induced aggregation is likely to be stimulated in SHRSP platelets, because protein kinase C activity in SHRSP platelets appears to be high.
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PMID:Changes in free calcium concentrations in platelets of SHRSP and WKY: its relationship to ATP releasing potencies and platelet aggregation activities upon stimulation of several reagents. 177 5

The development of hemodialysis treatment has remarkably improved the prognosis of chronic hemodialysis (HD) patients. However, as the patient's survival time is prolonged, vascular damages due to the abnormalities of calcium and lipid metabolism and hypertension has become the important complications in HD patients. In addition to coagulation and fibrinolysis, vascular endothelial function has been pursued to clarify the pathogenesis for occurrence of thrombosis in HD patients with more than ten years' duration. Twenty-two HD patients including twelve of less than ten years' duration and ten of more than ten years' were subjected to this study. Twelve healthy controls were also involved in this study. Fibrinopeptide A (FPA) and thrombin-antithrombin III complex (TAT) as indexes of coagulation, antithrombin III (AT III) as an index of coagulation inhibitor and D-dimer as an index of fibrinolysis were measured. A special attention has been focused in changes in the levels of tissue plasminogen activator (t-PA) activity and antigen and plasminogen activator inhibitor-1 (PAI-1) as indexes of fibrinolysis capacity, representing parameters of vascular endothelial functions. Levels of FPA, TAT and D-dimer were significantly higher in HD patients when compared with those in healthy controls. In particular, levels of FPA were significantly higher in HD patients with more than ten years' duration as compared to those in HD patients with less than ten years'. AT III values were significantly lower in HD patients with more than ten years' duration than those in healthy controls. T-PA activity and antigen levels were significantly lower in HD patients than those in healthy controls. T-PA activity levels were lower in HD patients with more than ten years' duration than those in HD patients with less than ten years'. Among HD patients, a significant negative correlation was found between t-PA activity and hemodialysis duration. PAI-1 values in HD patients were not significantly differ from those in healthy controls. These results suggest that in spite of increased coagulability, fibrinolytic capacity of vascular endothelium decreased in HD patients, and that the incidence is accelerated as hemodialysis duration is prolonged. Therefore, it is concluded that long-term HD patients are in the state of a higher risk of thrombosis.
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PMID:[Long-term hemodialysis and changes in variables of coagulation and fibrinolysis]. 177 13

Platelet aggregation to incremental doses of eight different platelet agonists (collagen, thrombin, platelet-activating factor [PAF], arachidonic acid [AA] plus epinephrine, the calcium ionophore A23187, ADP, phospholipase C [PLC], and 12-O-tetradecanoyl phorbol-13-acetate [TPA]) was compared in normal (N) and cyclic hematopoietic (CH) dogs. Platelet aggregation was defective with collagen, PAF, TPA, and possibly thrombin as agonists but normal when ADP, PLC, arachidonic acid plus epinephrine, and A23187 were used as agonists with CH platelets. In heterozygous CH dogs, platelet aggregation was intermediately defective when tested with collagen and PAF as agonists. Thromboxane B2 (TXB2) concentrations (mean +/- SD; pg/10(6) platelets), as measured by RIA, were similar in CH and normal dogs both prior to (CH: 7.6 +/- 7.0; N: 5.5 +/- 3.9) and after collagen stimulation (collagen: 141.3 +/- 42.5; 123.1 +/- 38.4). Granule storage pools of serotonin and platelet adenine nucleotides were markedly decreased in homozygous CH but not heterozygous CH dogs. Thrombin stimulated phosphorylation of 40- and 20-kd proteins in platelets from CH and normal dogs to an equal extent. However, collagen-stimulated phosphorylation of the 40- but not the 20-kd protein was significantly decreased in platelets from CH dogs. These data suggest that there is a biochemical defect in platelets from CH dogs that results in storage pool disease and decreased phosphorylation of a 40-kd protein.
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PMID:Characterization of platelet function in cyclic hematopoietic dogs. 189 69

The effect of 12-tetradecanoyl phorbol 13-acetate on the GTPase activity of Gi was investigated. Treatment with TPA did not alter basal GTPase activity of membranes or the stimulatory effect of prostaglandin E1 (putatively via Gs). In contrast, the phorbol ester markedly diminished stimulation of GTPase by agents whose receptors are coupled to Gi such as epinephrine (alpha-adrenergic action), platelet activating factor or thrombin. Pertussis toxin catalyzed ADP-ribosylation was also decreased in membranes from TPA-treated platelets as compared to the controls. It is suggested that the alteration in the hormonal activation of the GTPase activity of Gi is secondary to a perturbation in the receptor-Gi interaction.
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PMID:Activation of protein kinase C inhibits hormonal stimulation of the GTPase activity of Gi in human platelets. 190 Apr 75

Increased thrombogenesis observed in systemic lupus erythematosus (SLE) is derived from multiple mechanisms, including: Enhanced coagulation factor VIII:VWf activity, lupus anticoagulants, anti-phospholipid antibodies, acquired deficiencies of natural anti-thrombotic mechanisms (protein C, protein S, anti-thrombin III), and impaired fibrinolytic mechanisms. We studied the fibrinolytic mechanisms of 18 patients with systemic lupus erythematosus, selected carefully to avoid other possible causes of abnormalities in the fibrinolytic activity. Despite the fact that the euglobulin lysis time in steady state was normal in all instances, disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system were found in all SLE patients: TPA activity was undetectable in all cases, whereas it was above 0.4 IU/ml in a control group. In 72 percent of patients, the undetectable TPA activity was correlated with abnormally high PAI activity; PAI levels were normal in all members of the control group, their mean value being 0.74 versus 8.63 IU/ml for SLE patients (P less than .01). Coagulation protein C deficiency was found in 3 patients (17%). Even though within normal range, fibrinogen levels were significantly higher in SLE than in normal controls (219 versus 192 mg/dl, P less than .01) and plasminogen levels were significantly higher in SLE than in controls (117 versus 78.2%, P less than .01). Cross-linked fibrin derivatives (D-D dimers) were negative in all patients with SLE. Sixty-eight percent of SLE patients had high levels of antiphospholipid antibodies, but no correlation with the disturbances of the TPA/PAI system was found. It is concluded that most patients with SLE display severe abnormalities in the TPA/PAI anti-thrombotic system and that these abnormalities may be related to the lupus thrombophilia, apparently multifactorial in its origin.
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PMID:Disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system in systemic lupus erythematosus. 190 23

Effects of extracellular Na+ on platelet responses were examined. Cytoplasmic pH decreased by stimulation with thrombin, TPA and AA in Na(+)-containing buffer as well as in Na(+)-free buffer. Thrombin-induced aggregation and serotonin release were higher in Na(+)-containing buffer, but TPA- and A23187-induced responses exhibited lower values. Thrombin-stimulated platelet in Na(+)-free buffer started to aggregate by the addition of NaCl. Inhibition of thrombin-induced aggregation by indomethacin was apparently weaker than that by removal of Na+. These results suggest that the changes of platelet responses by removal of Na+ is due to the effect of Na+ ion itself, not by the inhibition of Na+/H+ exchanger, and that Na+ affects on mechanisms other than arachidonic acid mobilization.
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PMID:Changes of platelet functions by extracellular sodium ion. 190 98


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