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)

Extracts from uterine cervical and corpus cancers, but not from benign tumor or intact tissues tested, were found to contain a growth-promoting activity which induced the proliferation of human endometrial fibroblasts. Exposure of cultured fibroblasts to the cancer extracts increased the rate of [3H]thymidine incorporation in a dose-dependent manner. The activity was heat-labil, and not inacticated by removal lipid-soluble fraction, suggesting that the activity is associated with a protein. However, the cancer extract failed to stimulate phosphoinositide turnover. The substance(s) present in the uterine cancer extracts may activate endometrial fibroblasts proliferation through the transmembrane signaling mechanisms other than phosphoinositide turnover. The bindings of previously identified growth factors including somatomedine C, thrombin, insulin, fibroblast growth factor were not inhibited by the extracts. This is the first report to provide direct evidence that malignant uterine tumor may produce and secrete a putative growth factor-like peptide.
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PMID:A putative growth factor in extract from uterine cancers. 260 22

Treatment of cultured astrocytes from 2-day-old rat cerebral hemispheres with insulin, somatomedin C (IGF1), thrombin and acidic or basic fibroblast growth factors promoted a rapid activation of a cytosolic protein kinase (S6 kinase) which phosphorylates ribosomal protein S6. The phorbol ester (TPA) also triggered a rapid increase in S6 kinase activity. Two agonists of adenylate cyclase activity (forskolin and isoproterenol) and the cyclic AMP analog (dibutyryl cAMP) also stimulated the same S6 kinase. These observations support the idea that several pathways might promote the activation of the same entity that is regarded as one of the primary targets of signals elicited by growth factors.
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PMID:[A model for studying the transmission of information produced by certain growth factors: activation mechanisms of S6 kinase in cultured astrocytes]. 262 75

The human breast tumor cell line was separated by Percoll density gradient centrifugation into six different subpopulations, A to F, one of which (E) appears to contain the stem cells on the basis of several criteria (M. Resnicoff et al. 1987, Proc. Natl. Acad. Sci. USA 84, 7295. We now analyzed the response of the isolated subpopulations to insulin, thrombin, PGF2 alpha, estradiol, and 13-cis-retinal. We demonstrate that the first two growth factors stimulate [3H]thymidine incorporation in the more differentiated subpopulations (D and F), while PGF2 alpha has mitogenic activity in subpopulations C and D. In the absence of any added growth factor, estradiol has the extreme and transient capacity of allowing the stem cell to detach from the tissue culture dish and to grow in suspension as multicellular aggregates (MCF-7/SE cells). 13-cis-Retinal acts as a negative modulator of differentiation and protects the cells from the inhibitory and differentiation activity of Na-butyrate.
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PMID:Growth factors and hormones which affect survival, growth, and differentiation of the MCF-7 stem cells and their descendants. 264 48

The presence of heterogeneous erythroid progenitor cells, contaminant cells, or serum may alter erythroid colony development in vitro. To obtain highly purified colony-forming units-erythroid (CFU-E), we cultured partially purified human blood burst-forming units-erythroid (BFU-E) in methylcellulose with recombinant human erythropoietin (rHuEPO) for 7 d and generated cells that consisted of 30-60% CFU-E, but no BFU-E. A serum-free medium was used that allowed development of the same number of erythroid colonies as serum containing medium, but with a greater percentage of larger colonies. This medium consisted of delipidated crystalline bovine serum albumin, iron saturated transferrin, lipid suspension, fibrinogen, thrombin, Iscove's modified Dulbecco's medium/F-12[HAM], and insulin plus rHuEPO. When CFU-E were cultured in a limiting dilution assay and the percentage of nonresponder wells was plotted against cell concentration, both serum-free cultures and serum-containing cultures yielded overlapping straight lines through the origin indicating that CFU-E development did not depend on accessory cells and that insulin acted directly on the CFU-E. Human recombinant interleukin 3 (IL-3) and/or granulocyte-macrophage colony-stimulating factor had no effect on CFU-E growth, while they markedly enhanced BFU-E growth. Physiological concentrations of recombinant human insulin-like growth factor I (IGF-I) enhanced CFU-E growth in the absence of insulin and, together with rHuEPO in serum-free medium, provided a plating efficiency equal to that of serum-containing medium. Limiting dilution analysis in serum-free medium with IGF-I showed a straight line through the origin indicating that IGF-I also acted directly on the CFU-E and not through an effect on accessory cells. These data demonstrate that CFU-E do not require accessory cells, but do require IGF-I and/or insulin which act directly on the CFU-E.
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PMID:Human colony-forming units-erythroid do not require accessory cells, but do require direct interaction with insulin-like growth factor I and/or insulin for erythroid development. 265 78

We examined the level of 1,2-diacylglycerol and inositol phosphates in normal and EJ-H-ras-transformed BALB/3T3 fibroblasts by prelabelling the cells with [3H]glycerol, [3H]inositol, [14C]glucose, [14C]arachidonic acid, and [14C]palmitic acid. Steady-state level of inositol phosphates, however, was the same in control and transformed cells. Diacyglycerol labelling by [14C]arachidonic acid was the same in control and transformed cells. Insulin dramatically increased diacylglycerol labeling by [14C]glucose in normal cells, whereas it did not affect ras-transformed fibroblasts. Neurotransmitter-induced inositol lipid turnover was greatly enhanced in ras-transformed cells; conversely, platelet-derived growth factor and thrombin-stimulated normal cells to a greater extent than transformed fibroblasts. Taken together these results suggest that ras transformation may induce multifarious effects on signal transduction: it may cause de novo synthesis of diacylglycerol and subversion of neurotransmitter and growth factor receptor coupling to inositol lipid metabolism.
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PMID:Signal transduction in EJ-H-ras-transformed cells: de novo synthesis of diacylglycerol and subversion of agonist-stimulated inositol lipid metabolism. 266 28

1. Endogenous noradrenaline release from washed platelets incubated under resting conditions and in the presence of thrombin was examined in 14 normal subjects and 10 subjects with type 1 (insulin-dependent) diabetes. 2. Irreversible aggregation of platelets from both normal and diabetic subjects was induced by thrombin (0.3 unit/ml). Platelets from diabetic subjects were more sensitive than platelets from normal subjects, extents of aggregation being 89% and 76%, respectively (P less than 0.002). 3. Stimulation with thrombin (0.3 unit/ml) elicited marked platelet release of noradrenaline to the incubation medium in both normal and diabetic subjects. Supernatant noradrenaline concentrations obtained under thrombin-stimulated conditions did not significantly differ between normal and diabetic subjects. However, under resting conditions noradrenaline levels were significantly greater (+93%, P less than 0.02) for diabetic than normal subjects. 4. Measurement of platelet noradrenaline contents after thrombin stimulation revealed no difference between normal and diabetic subjects. Under resting conditions, however, platelet noradrenaline levels were significantly lower (-46%, P less than 0.02) for diabetic than normal subjects. Thus, in the diabetic subjects increased resting platelet efflux of noradrenaline is mirrored by a decreased platelet noradrenaline content. 5. A consequence of increases in resting catecholamine efflux may be enhanced platelet activity resulting in increased platelet aggregation.
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PMID:Platelet efflux of noradrenaline in patients with type 1 diabetes mellitus. 273 79

In vivo study of blood coagulation and fibrinolysis activities in non insulin dependent diabetes mellitus. The aim of the study was to investigate in vivo blood coagulation and fibrinolysis activities in a group of diabetic patients NIDDM with and without vascular complications. For this purpose we determined two sensitive indicators in vivo of blood coagulation and fibrinolytic activities such as fibrinopeptide A and B beta 15-42 respectively. Moreover, we computed the ratio between B beta 15-42 and fibrinopeptide A in order to investigate a possible imbalance in vivo between blood coagulation and fibrinolysis. Control groups were 15 healthy subjects and 28 non diabetic patients affected by atherosclerotic disease. Fibrinopeptide A and B beta values were significantly higher in the diabetic patients than controls but there was no difference between the former group and the atherosclerotic patients. Also, no correlation was found for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose levels. There was no difference in B beta, FPA and B beta/FPAr values for patients treated with insulin and for those treated with either hypoglycemic agents or diet. Our data indicate that in diabetic patients fibrinolysis activity is increased, but it cannot counterbalance thrombin activity which appears much more enhanced. Finally, the lack of correlation for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose suggests that blood coagulation and fibronolysis abnormalities are not related to the degree of blood glucose control.
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PMID:[Activity of the coagulation and fibrinolysis in non-insulin-dependent diabetes mellitus. In vivo study]. 277 95

Plasma from insulin-dependent diabetics shows an increased ability to specifically activate the (Na-K)ATPase from different sources. Several protease inhibitors like phenyl methyl sulfonyl fluoride, trypsin inhibitor, antithrombin III and aprotinin, produced a significant dose-dependent inhibition of the stimulatory effect produced by a 1/100 final dilution of plasma on the beef heart (Na-K)ATPase activity. Serine proteases employed at scalar concentrations in the ATPase medium gave a dose-dependent stimulation of the enzyme activity as did diabetic plasma. The maximum percent stimulation of the (Na-K)ATPase activity (about 60%) was reached by 0.56 microgram/ml of thrombin, 0.50 microgram/ml of kallikrein and 0.55 microgram/ml of trypsin. The protease-induced ATPase stimulation was significantly reduced by antithrombin III, trypsin inhibitor and by aprotinin. A partial purification of the activating plasma factor was obtained by eluting plasma on a heparin-Sepharose column. Two (Na-K)ATPase stimulating fractions were found, which eluted with 1.0 and 3.0 mol/l NaCl, respectively. Half-maximal stimulation of the enzyme occurred with 3.4 micrograms/ml proteins of fraction 1.0 mol/l and with 45 ng/ml proteins of fraction 3.0 mol/l, this last representing the most purified plasma fraction (about 8890-fold purification). The proteolytic activity of both plasma and purified plasma fractions was tested on Tos-Arg-OMe substrate which was hydrolyzed to a much higher degree by the most purified plasma fraction. Like the (Na-K)ATPase stimulation, the esterolytic activity was inhibited by protease inhibitors, the most effective to this regard being antithrombin.
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PMID:Identification and partial purification of a (Na-K)ATPase stimulating serine protease from plasma of insulin-dependent diabetics. 283 59

Stable expression of high levels of activated forms of Haras (T24) or v-Ki-ras by transfection of Chinese hamster lung fibroblasts (CCL39) yielded cells highly tumorigenic in nude mice. Two classes of transformed cells were distinguished, one with moderate p21 expression (10-fold increased) had retained growth factor dependency, the second with higher level of p21 (greater than 50-fold) appeared autonomous for growth. Neither class of transformants expressing Ki-ras or Ha-ras displayed a significant basal activity of polyphosphoinositide-specific phospholipase C, measured either in serum-starved cells or during exponential growth in the presence of growth factors of the tyrosine kinase family (EGF, FGF, insulin). In the growth-factor-dependent class of T24-Ha-ras-transfected cells (clone 39THaB), phospholipase C could be stimulated normally by serum, thrombin and AlF-4. In the more growth autonomous class (clones 39THaC and 39Ki9), release of inositol phosphates after stimulation with thrombin or serum was drastically reduced. This desensitization, apparently at the receptor level since the response to AlF-4 persisted, is, however, not specific to ras expression. We observed it to the same degree in polyoma virus-transformed CCL39 cells. Finally, expression of mutated forms of p21 ras did not abrogate the sensitivity of phospholipase C activation to pertussis toxin. We conclude that the transforming potential of activated forms of p21ras does not result from persistent activation of phospholipase C and that ras GTP-binding proteins cannot substitute for Gp.
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PMID:Deregulation of hamster fibroblast proliferation by mutated ras oncogenes is not mediated by constitutive activation of phosphoinositide-specific phospholipase C. 283

Three newly synthesized benzoic acid derivatives (terephthalic acid anilides, chalcone carboxylic acid, and azobenzene carboxylic acid), with a certain structural similarity to retinoic acid, were examined for their retinoid-like bioactivity and their capacity to bind to cellular retinoid binding proteins. Two in vitro systems were used to evaluate their retinoid-like bioactivity: inhibition of adipose conversion of ST 13 murine preadipose cells and growth promotion of murine sarcoma virus (MSV)-transformed 3T3 cells in serum-free culture. All three compounds tested inhibited ST 13 adipose conversion at nanomolar concentrations in a manner similar to classical retinoids such as retinoic acid. The growth-stimulating activity of these compounds on MSV-transformed 3T3 cells was one to two orders of magnitude greater than that of retinoic acid. Simultaneous treatment with these compounds and retinoic acid produced only a barely detectable additive effect, suggesting a common mechanism of action, whereas unrelated mitogens, thrombin, and insulin worked synergistically in combination with retinoic acid. None of the compounds competed with retinol for binding to cellular retinol binding protein. However, two of the three competed with retinoic acid for binding to cellular retinoic acid binding protein. This study provides evidence that the newly synthesized compounds should be included among the retinoids and that their strong biological activity will undoubtedly contribute to the biological and medical application of retinoids.
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PMID:Functional studies of newly synthesized benzoic acid derivatives: identification of highly potent retinoid-like activity. 283 39


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