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: UNIPROT:P15088 (mast cell)
14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N6,O2'-Dibutyryladenosine cyclic 3',5'-phosphate plus theophylline inhibited the growth of the mouse mast cell tumor line PY 815 both in vivo and in vitro. The inhibitory effect on growth in vitro was rapidly reversed following removal of the drugs. Growth inhibition was accompanied by reduced cell surface activity and increased cell-cell adhesion. The drug-treated cells accumulated distinct membrane-bound granules, which are characteristic of more mature mast cells. Treated cells also developed increased amounts of surface-associated acidic mucopolysaccharides. These results suggest that increased intracellular cyclic adenosine 3':5'-monophosphate causes mouse mastocytoma cells to decrease growth and elicits the expression of a more differentiated mast cell phenotype. The effect of the antileukemia drug, 4'-(9-acridinylamino)methanesulfon-m-anisidine, on cyclic adenosine 3':5'-monophosphate and adenosine 5'-triphosphate in mastocytoma cells is also reported.
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PMID:Regulation of growth of mouse mastocytoma cells. 16 78

Cell-free particulate preparations derived from sonicated, purified rat peritoneal mast cells can be radiolabeled with IgE. The IgE concentration-dependence and the kinetics of the binding reaction at pH 6.6 were very similar to those observed with intact mast cells. The number of IgE molecules bound per mast cell equivalent at saturation varied somewhat from one particulate preparation to the next and, on average, was about 50% of the binding capacity of the intact cells. Incubation of intact mast cells or of particulate fractions with low concentrations of IgE in serum-free media resulted in a decrease in the amount of bindable IgE which remained in the supernatants in excess over the amount of IgE which was bound to the cells. Specific binding of IgE to both particles and to intact cells at limiting IgE concentrations was stimulated up to approximately twofold by a variety of antibiotic, synthetic or high molecular weight (protein) protease inhibitors of which soybean trypsin inhibitor and p-nitrophenyl-p'-guanidinobenzoate were the most active. These substances also markedly protected the IgE, leaving more of it bindable to rat basophil leukemic cells in a second incubation. Binding to particulate fractions also occurred at pH 4.8 when bovine serum albumin was added to the incubations. The results are consistent with the view that normal peritoneal mast cells have a membrane-bound protease which has high selectivity for IgE.
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PMID:On the nature of the presumed receptor for IgE on mast cells. V. Enhanced binding of 125I-labeled IgE to cell-free particulate fractions in the presence of protease inhibitors. 61 23

A comparative autoradiographic study on the uptake and intracellular localization of 3H-leucine-, 3H-dopa-, 3H-dopamine- and 3H-ATP-derived radioactivity was performed in the mouse carotid body to investigate the metabolic features of the chief cell as a paraneuron. 3H-leucine-derived radioactivity representing recently synthesized peptides was demonstrated in all kinds of cells in the carotid body and surrounding area. The chief cell was less radioactive than the nerve cell in the superior cervical ganglion. In the electron microscope autoradiography, no accumulation of radioactivity could be demonstrated either in the Golgi area of the chief cell, where the membrane-bound particles were probably formed, nor in the periphery of the cells, where they were stored before their release. Incorporation of 3H-dopa-derived radioactivity representing recently synthesized catecholamines was specific to the chief cell, mast cell, and nerve cell in the superior cervical ganglion. In the chief cell the distribution of radioactivity was roughly identical with that of the large dense-cored vesicles. Striking accumulations of 3H-dopamine-derived radioactivity were demonstrated in the adrenergic nerve terminals in the perivascular space and the glomus complexes of the carotid body. Not all of the chief cells incorporated the 3H-dopamine-derived radioactivity. 3H-ATP derived radioactivity was demonstrated in all kinds of cells in the carotid body and surrounding tissues. In the chief cell, as in other kinds of cells, the highest radioactivity was seen in the nucleus. The present results suggest that, if the large dense-cored vike those membrane-bound particles in other paraneurons, contain peptides, monoamines and ATP, the turnover of these products as secretory materials is much slower in this cell than in such endocrine paraneurons as adrenal chromaffin cells and gut endocrine cells.
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PMID:An autoradiographic study of the mouse carotid body using tritiated leucine, dopa, dopamine and ATP with special reference to the chief cell as a paraneuron. 102 Oct 15

The presence of moderate amounts of histamine in the human placenta was confirmed (0.72 +/- 0.10 microgram/g wet weight), and the hitherto unknown storage site of this biogenic amine was elucidated. Mast cells were identified by their characteristic morphology, staining reactions and secretory activity measured in terms of histamine release. Human placental tissue contains 7.6 x 10(5) mast cells/g wet weight, identified by staining with toluidine blue or alcian blue, and these cells were positive for chloro-acetate-esterase. Light microscope studies of placental tissue stained with HRP-conjugated anti-human IgE demonstrated cells with a typical 'halo' effect indicating cell-bound IgE, and electron microscopy revealed cells containing membrane-bound electron dense granules. A single mast cell was calculated to contain approximately 1 pg of histamine. Enzymatic digestion of placental tissue with collagenase (1.5 mg/ml) yielded viable cell suspension. containing mast cells in a purity of 0.6% which exhibited a low spontaneous output of histamine (12%). Placental mast cells released histamine in a concentration dependent manner upon challenge with anti-human IgE and the calcium ionophore A23187. Also, unlike other human mast cells so far studied. with the exception of skin, those dispersed from human placenta were responsive to the polybasic secretagogue compound 48/80. These findings represent a novel source of human mast cells and, since placentas are readily available in quantity, such tissue is proposed as an ideal source of mast cells for biochemical and pharmacological use.
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PMID:A novel source of mast cells: the human placenta. 171 42

In order to define the role of Kit ligand (KL) growth factor encoded at the mouse steel (SI) locus in spermatogenesis, we have examined its production in Sertoli cells. As a measure KL growth factor bioactivity, the ability to support proliferation and maintenance of mast cells was used in co-culture with primary mouse Sertoli cells. On the sertoli cells derived from +/+ and Wv/Wv mice, +/+ mast cells proliferated and were supported for more than 2 weeks, but not W/Wv mast cells. In contrast, Sertoli cells from SId/SId mice could not support +/+ mast cell proliferation under similar conditions. The supportive effect required close-range interaction of Sertoli cells with cultured mast cells. These results indicate that Sertoli cells derived from +/+ and Wv/Wv but not SId/SId mutant mice produce biologically active KL growth factor as a membrane-bound form. The biologically active KL of Sertoli cells may also play an important role in germ cell growth and differentiation.
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PMID:Biologically active kit ligand growth factor is produced by mouse Sertoli cells and is defective in SId mutant mice. 172 63

We have carried out cytochemical and ultrastructural examination of human leukemic cells showing basophil/mast cell features derived from patients with acute myelogenous leukemia or basophilic crisis in chronic myelogenous leukemia. Leukemic cells in each case initially showed metachromasia with toluidine blue and various degrees of positivity for astra blue. Other cytochemical results showed considerable variety among cases. The number of granules increased in short-term culture in every case. Ultrastructurally, small membrane-bound granules with or without myelinoid bodies or glycogen particles were present in immature blasts, followed by production of other granule types. In some cases, leukemic cells before and after liquid culture contained the typical basophil granules with or without myelinoid bodies, but the matrix was more loose than normal. Granules showing whorl or scroll matrix profiles, which were typical for mast cells, were present in two cases. In one case, immature leukemic cells contained theta granules, and some mature forms after short-term culture contained typical basophil/mast cell granules as well as theta granules. Leukemic cells occasionally contained multivesicular granules predominantly. These results indicate that leukemic cells with basophil/mast cell features show a heterogeneous configuration and contain abnormal granules differing from normal ones. This abnormal granulopoiesis may be attributable to the results of leukemic events and may be a hallmark for recognition of leukemic basophils/mast cells.
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PMID:Abnormal granulopoiesis of leukemic cells with basophil/mast cell features. Cytochemical and ultrastructural observations. 175 19

Two peptides corresponding to the amino acid sequences 1-10 (N-terminal peptide) and 303-313 (C-terminal peptide) of the bovine heart mitochondrial phosphate carrier have been synthesized. After being coupled to ovalbumin, they were injected into rabbits to raise polyclonal antibodies. The specificity of the generated antibodies was tested by enzyme-linked immunosorbent assay (ELISA) and/or Western blot. Anti-N-terminal antibodies and anti-C-terminal antibodies exclusively reacted with the corresponding terminal peptide, they also reacted with the isolated phosphate carrier as well as with the phosphate carrier protein in mitochondrial lysates. Both anti-N-terminal and anti-C-terminal antibodies bound to freeze-thawed mitochondria, indicating that both termini of the membrane-bound phosphate carrier are exposed to the cytoplasmic side of the inner mitochondrial membrane. These immunological data were complemented with results concerning enzymatic cleavage of the membrane-bound phosphate carrier by carboxypeptidase A and by an arginine-specific endoprotease. Carboxypeptidase A markedly decreased the binding of anti-C-terminal antibodies to phosphate carrier in freeze-thawed mitochondria. Arg-endoprotease cleaved the phosphate carrier in inside-out submitochondrial particles, but not in right-side-out particles, yielding two fragments of similar apparent molecular weight (Mr approximately equal to 14.5K), which were immunodetected only by the anti-N-terminal antiserum, and a fragment of Mr approximately equal to 17K which was detected only by the anti-C-terminal antiserum. It appears, therefore, that Arg-endoprotease cleavage sites of the phosphate carrier are present only at the matrix side of the inner mitochondrial membrane, at Arg-140 and/or Arg-152.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transmembrane topography of the mitochondrial phosphate carrier explored by peptide-specific antibodies and enzymatic digestion. 203 64

Dendrotoxin and mast cell degranulating peptide are highly potent convulsant polypeptides from mamba snake and bee venoms, respectively. Electrophysiological techniques and binding assays were used to study their interaction with fast-activating, voltage-dependent potassium channels in rat neurons. Intracellular recordings in sensory ganglion cells showed that mast cell degranulating peptide blocks the same slowly inactivating potassium current as dendrotoxin but with lower potency, the respective IC50 values in sensory A neurons of nodose ganglion being 2.1 nM and 37 nM. In contrast, the transient potassium current (IA) in superior cervical ganglion neurons was unaffected by either toxin, highlighting the heterogeneity of these potassium channels and the selective action of the toxins. Using biologically active 125I-labelled derivatives of dendrotoxin and beta-bungarotoxin (a related snake protein), the binding of mast cell degranulating peptide to two subtypes of high-affinity acceptors in rat cerebrocortical synaptosomal preparations was examined. Mast cell degranulating peptide antagonized the specific binding of both radioiodinated toxins to each of the acceptor species, in the membrane-bound state; additionally, [125I]dendrotoxin binding in detergent-solubilized extracts was, likewise, blocked by mast cell degranulating peptide. Notably, the observed inhibitory constants (KI) for mast cell degranulating peptide were appreciably larger than for dendrotoxin, consistent with their different efficacies in blocking the potassium conductances. It is concluded that the specific interaction of this apian polypeptide with dendrotoxin acceptors must underlie its selective action on potassium conductances, emphasizing a functional relationship between these membrane acceptors and the potassium channel variants, sensitive to both dendrotoxin and mast cell degranulating peptide.
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PMID:Mast cell degranulating peptide and dendrotoxin selectively inhibit a fast-activating potassium current and bind to common neuronal proteins. 244 37

Active tumor promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or membrane-diffusible synthetic diacylglycerols such as 1,2-dioctanoyl-sn-glycerol (DiC8), which specifically activate protein kinase C (PKC), inhibited the agonist-mediated rise in cytosolic calcium [(Ca2+)i] in a mast cell line (PB-3c) and human platelets. TPA inhibition of agonist-mediated calcium transient in platelets was readily reversed by the PKC inhibitor staurosporine. In contrast to DiCs, only active tumor promoters induced a time- and dose-dependent translocation of cytosolic PKC to membranes as determined both enzymatically or by immunoblotting. However, the concentration of TPA required to induce a half-maximal subcellular redistribution of immunodetectable PKC activity was an order of magnitude greater than the half-maximal dose required to inhibit the intracellular rise in (Ca2+)i. Thus, activation of PKC seems not to be exclusively coupled to its translocation to membranes, suggesting that translocation of PKC is mainly involved in the down-regulation of PKC. Down-regulation of immunoprecipitable PKC was studied in various human breast cancer cell lines that display differential growth inhibitory responses toward the tumor promoter. TPA induced translocation of [35S]methionine-prelabeled cytosolic 80 kDa PKC to membranes followed by complete degradation of the enzyme (t1/2 = 2 h) without affecting PKC synthesis. During prolonged TPA exposure, 20-80% of total 80 kDa PKC of control cells was still synthetized as a membrane-bound 74/80 kDa PKC doublet. Although both proteins lacked PKC activity and phorbol ester binding, they revealed structural similarity with the active 80 kDa PKC form of untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of protein kinase C (PKC) in short- and long-term cellular responses: inhibition of agonist-mediated calcium transients and down-regulation of PKC. 246 82

Paraneurons are receptosecretory cells producing substances of neurons. Like neurons, they are characterized by membrane-bound granules and vesicles which contain bioactive (and inactive) peptides, amines or other classic messengers, adenine nucleotides and acidic carrier proteins including chromogranins. The cell-biological significance of the carrier proteins in the secretory granules and the utility of immunohistochemical detection of chromogranins as reliable markers of paraneurons are emphasized. Cells "ectopically" producing bioactive peptides and/or amines, including ANP producing muscle cells of the heart, do not contain chromogranin immunoreactivity. The boundary between the neuron and paraneuron and that of the paraneuron are unclear because the cells comprise gradational spectra from typical ones to atypical ones. It is arbitrary whether to include the mast cell in the paraneurons, although it seems reasonable to exclude it by defining a paraneuron as being epithelial in nature.
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PMID:Present status of paraneuron concept. 251 Jul 74


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