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)

Lipoprotein(a) (Lp(a)) has been established as an important independent risk factor for the development of cardiovascular disease. Apolipoprotein(a), together with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in vitro and ex vivo experiments. We determined the correlations between Lp(a) and other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in 54 patients with essential hypertension, in 65 non-insulin-dependent diabetic patients and in 116 insulin-regulated diabetic patients. Signs of activated coagulation and increased reactive fibrinolysis were found in all three patient groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL-cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These data show that Lp(a) concentrations are not related to coagulation or fibrinolysis parameters in hypertensive or diabetic patients and confirm the presence of an activated coagulation system in these patient groups.
...
PMID:Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients. 138 33

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)
...
PMID:Protein phosphorylation and intracellular free calcium in platelets of patients with essential hypertension. 157 40

The effects of erythropoietin (EPO) on cytosolic free calcium concentration ([Ca2+]i) in platelets of 20 essential hypertensive patients (HT) and of 25 normotensive subjects (NT) were investigated using the fura2 technique. In resting platelets [Ca2+]i were not significantly higher in HT compared to NT (74.3 +/- 7.8 nM vs 59.8 +/- 7.0 nM, mean +/- SEM). Addition of EPO significantly increased [Ca2+]i in HT compared to NT (13.8 +/- 5.3 nM vs 0.9 +/- 1.9 nM, p less than 0.01). EPO increased the amount of calcium in intracellular stores. This was confirmed independently using thrombin-induced changes of [Ca2+]i in a calcium-free medium and using chlorotetracycline as a marker of stored calcium. After preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (306.1 +/- 30.0 nM vs 407.7 +/- 35.7 nM, p less than 0.05). In a calcium-free medium after preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (54.7 +/- 11.8 nM vs 100.9 +/- 10.5 nM, p less than 0.05) indicating lower storage capacity in HT. It is concluded that elevated response to EPO may provide a powerful tool to evaluate diagnosis and underlying pathophysiological mechanisms in essential hypertension.
...
PMID:Erythropoietin induced transmembrane calcium influx in essential hypertension. 161 80

To gain insight into the mechanisms that could account for the augmentation of cellular reactivity in primary hypertension, we have examined some of the biochemical events which are implicated in the transmission of mitogenic signal as well as in cell reactivity. This study focussed on phospholipase C, protein kinase C and GTP-binding proteins (G-proteins), in response to thrombin or arginin-vasopressin (AVP). Cultured fibroblasts prepared from the adventitia of thoracic aorta of spontaneously hypertensive rat (SHR) were used as cell models and were compared with fibroblasts prepared from controls Wistar-Kyoto (WKY) rats. The mitogenicity of each agonist was estimated by measuring the incorporation of 3H-thymidine into the newly synthesized DNA. The agonist-induced phospholipase C activity was evaluated by measuring the production of 3H-inositol phosphates in cells prelabeled with 3H-inositol. The influence of protein kinase C and that of G proteins on the mitogenesis in cells stimulated by thrombin or AVP was determined by pretreating cells with phorbol 12-myristate, 13-acetate (TPA) and pertussis toxin, respectively. Kinetics and dose response studies have demonstrated that in response to thrombin and AVP, the phospholipase C activity and the incorporation of 3H-thymidine were significantly higher in the fibroblasts derived from SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Activation mechanisms by thrombin and vasopressin of fibroblasts in spontaneously hypertensive rats]. 195 75

In primary hypertension, phospholipase C (PLC) is hypersensitive in several target tissues (platelets, vascular smooth muscle cells, aortic fibroblasts). Protein kinase C (PKC) and myosin light chain kinase (MLCK), which are physiologically activated by PLC-triggered second messengers (diacylglycerol and Ca2+ ions, respectively), phosphorylate specific proteins closely involved in the cell functional responses. In this study, we have examined and compared between platelets of spontaneously hypertensive rats (SHR) and their normotensive controls Wistar-Kyoto (WKY), the patterns of protein phosphorylation obtained either with the receptor-mediated agonist thrombin (i.e. which acts via PLC) or with direct activators of the protein kinases, PKC and MLCK. Activation by thrombin of 32P-prelabeled platelets induced incorporation of radioactivity into two proteins, P20 (myosin light chain) and P47. The curves obtained when platelets were challenged with either increasing doses of thrombin (0.025-0.3 U/ml) for 20 sec or with a low dose of the agent (0.1 U/ml) for up to 1 min, revealed that phosphorylation of the target proteins of PKC (P47) and of MLCK (P20) were significantly enhanced in platelets of SHR compared to WKY. In contrast, direct activation of PKC by phorbol ester and of MLCK by the calcium ionophore A23187 evoked the selective phosphorylation of the respective target proteins, P47 and P20, to a similar extent in platelets of SHR and WKY. Taken together, these results demonstrate that a physiological agonist (thrombin) induces an enhanced phosphorylation of intracellular proteins in platelets of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Increased phosphorylations of proteins involved in the expression of the physiologic response of platelets in SHR rats]. 212 75

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

It was reported that in essential hypertension, basal platelet free cytosolic (Ca)i measured with the fluorescent dye Quin 2, is elevated, but increases normally after thrombin stimulation. These data, were interpreted to suggest that plasma membrane fluxes are altered but the release of internal Ca2+ stores is intact. Previous studies have shown that Quin 2 inhibits Ca2+ release from internal stores following thrombin (T)-stimulation. Thus, we reassessed resting and T-stimulated platelet (Ca)i using the fluorescent dyes Fura 2 or Quin 2 in 11 subjects, 5 controls and 6 hypertensives. Mean basal (Ca)i with Quin 2 in controls was 138 +/- 15 nM vs 114 +/- 11 nM in hypertensives, (NS). By contrast, in the same platelet preparation (Ca)i with Fura 2 was higher in hypertensives than controls, 217 +/- 27 nM vs 120 +/- 4 nM, P less than .05. Blood pressure was correlated to (Ca)i obtained with Fura 2, R = 0.55. Thrombin 0.5 U/ml added to platelets in Ca-free media caused a multiphasic rise in (Ca)i with Fura 2. Although the absolute rise in (Ca)i in controls (592 +/- 104 nm) vs hypertensives (512 +/- 60 nm) did not differ, the % rise was less in hypertensives. Thus, 1) in the same population a higher resting (Ca)i was detected in platelets from essential hypertensives with Fura 2, but not with Quin 2; and 2) Ca2+ release from internal stores is altered in hypertension. Thus, Fura 2 is superior to Quin 2 in evaluating platelet (Ca)i.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Basal and stimulated cytosolic platelet calcium in essential hypertension. 233 78

The sympathetic nervous activity contributes to the pathophysiology of essential hypertension in an early phase and in younger patients mainly through increased beta-adrenoceptor-mediated functions and in a later phase and in older patients in whom beta-adrenoceptor-mediated functions are blunted, through increased alpha-adrenoceptor-mediated and calcium-influx-dependent vasoconstriction. Intracellular free calcium concentration is elevated in platelets of hypertensive patients and relates directly to the degree of their blood pressure, likely reflecting increased intracellular calcium concentration in vascular smooth muscle cells. A sympathetic factor is suggested further by the enhanced alpha 1-and alpha 2-adrenoceptor-mediated and calcium influx-dependent, vasoconstriction both of which are normalized by antihypertensive treatment in parallel with a normalization of intracellular free calcium and of the increased adrenaline sensitivity of platelets. The higher sensitivity to adrenaline for thrombin-induced calcium increases in platelets of hypertensive patients indicates potentiation of calcium influx (and mobilization from intracellular stores) by adrenaline, a mechanism that is mediated by alpha 2-adrenoceptors. As this effect is more pronounced in younger patients, increased adenylate cyclase sensitivity may prevail in the early and alterations in calcium influx-dependent mechanisms in the later phase of essential hypertension. The transition into a hypertensive state with reduced-reflex cardiovascular counterregulation codetermines the antihypertensive effectiveness of calcium antagonists in these patients.
...
PMID:Adrenoceptors, calcium, and vasoconstriction in normal and hypertensive humans. 241 75

In spontaneously hypertensive rats (SHR), enhanced activity of phospholipase C (PLase C) has been reported in various cells and tissues. In particular, the increased PLase C activity of platelets has been described as being involved in the hyperactivity to thrombin exhibited by these cells in SHR and in some patients with essential hypertension. In order to determine the relationship between such an enzymic abnormality and hypertension, the PLase C activity of platelets was investigated in various models of experimental hypertension, i.e. Dahl rats and DOCA-salt hypertensive rats. PLase C activity was determined by measuring the thrombin-induced 32P-phosphatidic acid (32P-PA) formation from 32P-prelabeled platelets. In parallel, experiments on the platelet reactivity was assessed by measuring the thrombin-induced serotonin secretion from 3H-serotonin prelabeled platelets. In Dahl salt-resistant rats (DR), the blood pressures were 123 +/- 6 and 118 +/- 7 mmHg for animals fed a low (0.3 p. 100) and high (4 p. 100) salt diet, respectively; the blood pressures of Dahl salt-sensitive rats (DS) were 159 +/- 6 and 202 +/- 11 mmHg, respectively. Hypertensive rats of the DOCA/salt--treated group exhibited a blood pressure of 210 +/- 8 mmHg compared with 137 +/- 4 mmHg for those of the control group. At rest (ie before stimulation) the platelets of all groups of animals behave similarly with respect to the incorporation of 32P and its metabolism into phospholipids as well as the uptake of serotonin. These data indicate therefore that platelets were in a similar quiescent status.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Phospholipase C hypersensitivity in hypertensive rats results from innate and acquired factors]. 251 Jun 65

Phospholipase C activity governs translocation of Ca2+ from intracellular sites of storage via IP3 (inositol triphosphate) and cell differentiation and growth via DG (diacylglycerol). Phospholipase C responsiveness to various agonists (thrombin, angiotensin II, growth factor) was shown to be increased in various tissues of SHR as compared to WKY (platelets, aortic cultured smooth muscle cells, aortic fibroblasts). The constancy of the response and its physiological significance suggest that this membrane biochemical change plays a crucial role in the pathogenesis of hypertension. Phospholipase C responsiveness was also tested in platelets of untreated hypertensive patients. Half of the sample exhibited an hyperreactivity similar to that observed in SHR rats. This finding confirms the heterogeneity of human essential hypertension and suggests that a proportion of patients have a biological pattern close to that of SHR.
...
PMID:[Oncogenes and arterial hypertension]. 267 13


1 2 3 4 Next >>

---