Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboplastin production in human monocytes gains steadily increasing significance as a pathogenetic factor in relation to human disease. A vast variety of stimuli can cause the induction of thromboplastin synthesis in monocytes, apparently through plasma membrane perturbation. Some of the possible signal compounds conveying information from the membrane to the intracellular-responding apparatus have been studied. Available data allow the conclusion that changes in intracellular concentrations of Ca2+, cyclic nucleotides and arachidonic acid metabolites as well as transmethylation reactions are of importance and modulate the integrated response which leads to increased synthesis and insertion of apoprotein III (the protein component of thromboplastin) in the plasma membrane.
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PMID:Intracellular signal mechanisms in induction of thromboplastin synthesis. 608 14

Mouse placental cells are probably constitutive producers of the thromboplastin apoprotein in vitro. The effect of cyclic AMP-elevating compounds on their expression of thromboplastin activity has been studied. Dibutyryl cyclic AMP, the phosphodiesterase inhibitor Ro 20-1724 and the adenyl cyclase stimulator forskolin all decrease the synthesis of thromboplastin. Prostaglandin E2 and the phosphodiesterase inhibitor butyl-methyl-xanthine have a biphasic dose dependent effect. A stimulation was observed at low concentrations, whereas higher doses decreased the synthesis of thromboplastin. Adrenaline had no effect. Combination of two compounds, each at maximally inhibiting concentration gave no significant additive inhibitory effect, showing that they probably act via the same pathway.
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PMID:Regulation of thromboplastin synthesis in mouse placental cells in vitro. 619 44

12-O-Tetradecanoylphorbol 13-acetate (TPA), phorbol 12,13-diacetate and phorbol 12,13-didecanoate were all potent inducers of thromboplastin activity in human monocytes in vitro, whereas 4 alpha-phorbol 12,13-didecanoate and 4 alpha-phorbol had no such effect. A concomitant increase in titrable apoprotein III antigen was found (apoprotein III is the protein component of thromboplastin). The increase was inhibited by cycloheximide and actinomycin D and partly by alpha-amanitin. The increase of thromboplastin activity was therefore most likely due to synthesis de novo of apoprotein III. The response was approximately halved in the absence of serum or Ca2+. Retinol had a weak inhibitory effect, and retinoic acid was inhibitory only at concentrations that also induced signs of cytotoxicity. TPA caused an initial rise in monocyte cyclic AMP concentration of about 90-120 min duration. No increase in 45Ca2+ influx was induced over 2 h. Good correlation exists between induction of apoprotein III synthesis in monocytes in vitro and mouse skin-tumour promotion in vivo by the various phorbol derivatives. Substances inactive in tumour promotion do not induce the synthesis of apoprotein III. General activating and cytotoxic effects of TPA were monitored by determining release of lysozyme, beta-glucuronidase and lactate dehydrogenase.
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PMID:Phorbol esters induce synthesis of thromboplastin activity in human monocytes. 627 36

Increasing evidence [1, 2, 3] demonstrates the clinical importance of monocyte thromboplastin synthesis in the pathogenesis of thrombosis and disseminated intravascular coagulation. Among the first to describe this was the group of the late F Josso [4, 5]. In addition, monocytes and macrophages appear to contribute to fibrin deposition in inflammatory lesions [6, 7]. Several procoagulant substances have been reported to appear in monocyte cultures. Among these, thromboplastin is the most potent and probably also the most important and well studied. Based as it is on our own work, this brief review will deal only with thromboplastin. It is a phospholipid-protein complex, consisting in human material of one species of protein (apoprotein III) mol. wt. approximately 52,000 surrounded by phospholipids [8] in an optimal molecular ratio of apoprotein:phospholipids of approximately 1:80 [9]. Apoprotein III is an integral membrane glycoprotein which apparently is located mainly on the outside of the plasma membrane. The molecular weight has recently been confirmed in our laboratory by Western blotting, using a monoclonal antibody to apoprotein III developed here (Johnsen, unpublished).
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PMID:The role of cellular cooperation in thromboplastin synthesis. 636 91

The role of protein moiety of tissue thromboplastin during its specific enzymatic modification by papain was studied. Treatment with papain was followed by a decrease of the number of binding sites for factor X on the surface of factor III. The ability of the remaining sites to bind factor X and to form prothrombinase complexes did not change thereby. The specific interaction of thromboplastin with the factors coupled with the external blood coagulation system are based on asymmetric distribution of phospholipids and apoprotein in the cell membrane.
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PMID:[Modification effect of the protein component of tissue thromboplastin (factor III) on its interaction with factors VII and X]. 646 43

Endothelial cells (EC) in culture produce a procoagulant identified as thromboplastin when stimulated with 12-O-tetradecanoyl-phorbol-13-acetate, phytohemagglutinin, endotoxin, thrombin, histamine or epinephrine. Inducible thromboplastin generation most likely depends on de novo synthesis of RNA and the protein component of thromboplastin, apoprotein III. It is further probably regulated by intracellular mechanisms involving cAMP, transmethylation and calcium ions. The EC thromboplastin response is enhanced in lymphocyte-EC and platelet-EC cocultures and thromboplastin becomes partly available on the cell surface. Levels of procoagulant activity are reached which clearly may be of clinical importance if similar levels appear in vivo.
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PMID:Thromboplastin synthesis in endothelial cells. 653 8

The hypercoagulable state in pregnancy is partly caused by the increased activity of factor VII in plasma. We demonstrate here that this activity is reduced to levels similar to those in plasma from non-pregnant women by highly purified phospholipase C from Bacillus cereus, i.e. the activity increase is due to a circulating complex of factor VII and a phospholipase C-sensitive compound. Phospholipase C had no effect on the levels of factor II and X in blood from pregnant women. This novel form of activated factor VII is not inhibited by an antiserum to the protein component of thromboplastin (apoprotein III). By gel filtration of plasma from pregnant women on Sephadex G-100 the phospholipase C-sensitive complex was partly separated from non-phospholipase sensitive factor VII also present in the same plasma.
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PMID:The coagulation factor VII in pregnancy. 660 66

Tissue factor (tissue thromboplastin, factor III), an initiator of coagulation, has been purified 142,000-fold to homogeneity from bovine brain. The protein is an integral membrane glycoprotein with an apparent molecular weight of 43,000 as judged by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The apoprotein was first purified by extraction with Triton X-100 and repeated preparative polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Antiserum was produced against a few micrograms of purified apoprotein and was used to construct an immunoadsorbent column. The column was then used for affinity purification of the apoprotein directly from the Triton X-100 extract, thereby significantly increasing the amount of purified protein produced. The purification scheme may be generally useful for the rapid and large scale purification of membrane proteins. Tryptic digestion of the apoprotein in Triton X-100 cleaved a peptide of approximately 3000 daltons without affecting the activity. The activity was recovered directly from stained SDS polyacrylamide gels, and the profile of recovered activity corresponded directly with the stained bands. The activity shifted along with the protein band following tryptic digestion, thus demonstrating that the protein observed on the gels is tissue factor. The coagulant activity of the purified apoprotein was reconstituted by the addition of phospholipid. Optimal activity was observed at phospholipid to protein ratios (w/w) greater than 450:1.
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PMID:Purification and characterization of bovine tissue factor. 679 May 39

Immune complexes induced the synthesis of apoprotein III, the protein component of tissue thromboplastin (tissue factor), in human monocytes cultured in vitro. The response was maximal (11.1 +/- 1.7 fold increase (mean +/- SEM) when immune complexes were formed at antigen/antibody equivalence. Immune complexes formed with the antigen-binding fragments (F(ab')2) of immunoglobulins induced a 4.7 +/- 1.4 fold activity increase, suggesting that another signal mechanism in addition to the Fc-receptor may be involved.
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PMID:Thromboplastin (factor III) activity in human monocytes induced by immune complexes. 680 71

Endothelial cells from human umbilical veins produce a procoagulant identified as thromboplastin (tissue factor, factor III) when stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA), phytohaemagglutinin (PHA) or endotoxin, Inducible thromboplastin synthesis (i.e. synthesis of the protein component of thromboplastin, apoprotein III) was totally inhibited by cycloheximide and actinomycin D, indicating that de novo protein and RNA syntheses are necessary. Serum enhanced the induced apoprotein synthesis. Of the total thromboplastin activity in homogenates of stimulated endothelial cells, about 50--70% was available on the cell surface for interaction with other coagulation factors, inactivation by trypsin and neutralization with antiserum against apoprotein III. Induced synthesis of thromboplastin in endothelial cells was 2--7-fold enhanced by the presence of several other cell types in optimal ratio 4--10 cells per endothelial cell. Some of these cell types were themselves thromboplstin producers (U-937, U-937-4), some were not inducible (lymphocytes, granulocytes and the lymphoblast lines Daudi and Molt 4). This enhancing effect was also seen with cell-free culture supernatants, but these were generally somewhat less effective than the intact cells. Supernatants derived from cells cultured in the presence of TPA, PHA or endotoxin were in most cases more effective than supernatants from unstimulated cells.
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PMID:Cellular cooperation in endothelial cell thromboplastin synthesis. 684 29


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