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

Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because 5-amino-4-imidazolecarboxamide riboside (AICA riboside) has been shown to alter adenosine metabolism and accelerate the repletion of ATP pools in other tissues, its effects on mast cell function were examined. Neither simultaneous addition of A23187 and AICA riboside nor a 1-hr preincubation with AICA riboside altered mast cell beta-hexosaminidase release to an appreciable degree. However, mouse bone marrow-derived mast cells cultured for 2 or more days in the presence of 1-100 microM AICA riboside exhibited a markedly attenuated mediator release response to A23187 compared to control cells with or without the additional presence of adenosine. IgE-mediated leukotriene C4 generation from AICA riboside-exposed mast cells was even more profoundly inhibited without affecting cell viability or resting mediator content. An unusual ribonucleotide triphosphate previously identified in folate-depleted cells, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-triphosphate (ZTP), has been identified in AICA riboside-treated mast cells as well. Although the mechanism of this global inhibition of mast cell mediator release by chronic AICA riboside treatment is not clear, alterations in mast cell purine metabolism may prove to be important in the treatment of allergic diseases.
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PMID:Inhibition of mast cell mediator release by 5-amino-4-imidazolecarboxamide riboside. 294 80

A new model system for studying biochemical reactions in mast cell plasma membranes was developed. Particles termed cytoplasts consisting of organelle-depleted cytoplasm surrounded by an intact plasma membrane were formed from cytochalasin B-treated mast cells ultracentrifuged through a discontinuous Ficoll gradient. Two cytoplasts were formed per mast cell and 95% were recovered. Mast cell cytoplasts had a mean diameter of 3.2 microns with a median volume of 38 microns 3. Enzyme marker studies indicated that subcellular recoveries in the mast cell cytoplast were: plasma membrane = 16%, cytoplasm = 39%, nucleus = 1.1%, granule = 0.5%. Analysis of IgE receptors indicated that mast cell cytoplasts retained the normal asymmetric orientation of the plasma membrane. Mast cell cytoplasts synthesized ATP, incorporated labeled fatty acids into complex lipids and retained fluorescein after deacylation of diacetylfluorescein. The quantity of cAMP (adenosine 3':5'-cyclic monophosphate) maintained in mast cell cytoplasts was 0.0304 pmol/10(6) original mast cells. Cytoplasts offer the opportunity to study plasma membrane and cytoplasmic biochemical events that occur during stimulation in a relatively physiologic environment.
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PMID:Preparation and characterization of mast cell cytoplasts. 302 28

In order to identify regulatory steps in leukotriene synthesis, the biochemical characteristics of a 5-lipoxygenase activity in the 100,000 xg supernatant from sonicates of cells of an IL-3 dependent murine mast cell clone, MC-9 were determined. Principal products from exogenous 14C-arachidonic acid were identified as leukotriene B4, diastereomeric 5,12-dihydroxy-eicosatetraenoic acids (5,12 diHETEs) 5-hydroperoxy and hydroxyeicosatetraenoic acids (5-HPETE and 5-HETE) as well as a novel metabolite 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). The crude lipoxygenase activity had a pH optimum of 6.9 and was highly dependent upon added Ca++. The effective Ca++ concentration for 50 per cent activation (EC50) was 3 microM. Activity was also stimulated by ATP (EC50 = 160 microM). The cytosolic 5-lipoxygenase activity exhibited a biphasic concentration dependence for arachidonic acid with maximum product formation occurring at 35 microM (ca. 20 nmole/mg/4 min). The lipoxygenase activity exhibited apparent lag phase kinetics which were more pronounced at low protein concentrations (0.3 mg/ml). In addition, the lag phase was greatly accentuated by the addition of a hydroperoxide scavenging system consisting of glutathione (1 mM) plus glutathione peroxidase (0.4 unit/ml). In contrast, addition of any of several hydroperoxides, i.e. 5-,8-,9- or 15-HPETE (EC50 ca. 1 microM), but not the corresponding alcohols (5-HETE and 15-HETE), shortened the lag phase. These results show that the 5-lipoxygenase requires hydroperoxide for activation and that cellular level of hydroperoxides may be an important factor regulating leukotriene synthesis.
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PMID:Modulation of the 5-lipoxygenase activity of MC-9 mast cells: activation by hydroperoxides. 309 36

ATP (as the tetrabasic acid, ATP4-) applied externally to rat mast cells causes the formation of lesions which permit influx and efflux of low molecular weight, normally impermeant aqueous solutes. To monitor membrane permeabilisation we have used two fluorescent dyes, ethidium which stains the nucleus, and TMA-DPH which stains the cytosolic surfaces of intracellular membranes following entry into the cells Permeabilisation by ATP is not affected by the metabolic status of the cells, and is maintained at temperatures as low as 8 degrees C. We have tested the ability of 30 structural analogues of ATP to effect mast cell permeabilisation. The analogues include those having substituents in the 2- and 8-positions of the purine ring, structural and optical isomers of the ribose sugar, and variations in the triphosphate chain. The pattern of selectivity displayed by the rat mast cell ATP4- receptor is distinct from those characteristic of the P1 purinoceptor for adenosine and the P2X and P2Y purinoceptors for adenine nucleotides.
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PMID:Characterisation of the ATP4- receptor that mediates permeabilisation of rat mast cells. 337 7

Mouse bone marrow-derived mast cells passively sensitized with monoclonal IgE released paf-acether (platelet-activating factor) and beta-hexosaminidase when challenged with the specific antigen. The formation and the release of paf-acether followed an early increase in the activity of the acetyltransferase, the main enzyme in paf-acether biosynthesis. The antigen-induced activation of the acetyltransferase was dependent on physiologic temperature and on the presence of Ca2+. By using microsomal fractions from unchallenged and challenged mast cells, the Vmax values were 3.5 and 12.0 nmol/min/mg of protein, respectively, whereas in both cases a Km value for acetyl-coenzyme A of 172 microM was measured. The stimulation of acetyltransferase could be mimicked in vitro under experimental conditions which favor phosphorylation, i.e. adding ATP and Mg2+ to lysates from unchallenged mast cells. In contrast, ATP and Mg2+ were uneffective on lysates from challenged cells that exhibited high level of acetyltransferase activity, suggesting that phosphorylation of the enzyme already took place at the time of cell stimulation. Moreover, addition of alkaline phosphatase to microsomal fraction obtained from either antigen-challenged mouse bone marrow-derived mast cells or unchallenged cells, resulted in 52% and 43% loss of acetyltransferase activity, respectively. Phorbol myristate acetate treatment of cells doubled the enzyme activity supporting the phosphorylation hypothesis. Thus, we report on the immunologic activation of a key enzyme for paf-acether synthesis and on the mechanism of this activation in a pure mast cell population. A link between bridging of IgE receptors and the activation of an enzyme critical to the formation of a lipid mediator is thereby evidenced.
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PMID:Biosynthesis of paf-acether. IX. Role for a phosphorylation-dependent activation of acetyltransferase in antigen-stimulated mouse mast cells. 358 83

We have identified in soluble extracts of rat heart, a 500 000 dalton sulfhydryl-dependent protease which degrades globin and casein to acid-soluble peptides at an alkaline pH optimum. This enzyme was purified more than 1700-fold with respect to the postmicrosomal supernatant. On the basis of various catalytic and biochemical properties the enzyme appears similar to a recently described cytoplasmic protease in rat liver. Protease activity in vitro was stimulated up to 3-fold by physiologic concentrations of ATP and to a lesser extent by some other phosphate-containing compounds. Unlike some alkaline proteases reported in heart tissue, this high molecular weight protease was identified in extracts from isolated cardiac myocytes and in extracts from hearts of rats treated with the mast cell degranulating agent Compound 48/80. Thus, the identification of the protease in heart does not appear to be accounted for by mast cell contamination.
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PMID:Identification of a high molecular weight alkaline protease in rat heart. 634 10

The effect of diethylstilbestrol, a synthetic estrogen, on mast cell secretion was investigated. The results showed that 50 microM diethylstilbestrol inhibited histamine release from rat peritoneal mast cells in the presence and absence of glucose, but did not affect 45Ca uptake stimulated by concanavalin A. Diethylstilbestrol also inhibited histamine release induced by compound 48/80, exogenous ATP, or ionophore A23187. Since estradiol benzoate, hexestrol and daidzein were not inhibitory, the inhibitory action of diethylstilbestrol must be independent of its estrogenic activity. The ATP content of mast cells decreased to less than 0.1 nmol/10(6) cells on treatment with 50 microM diethylstilbestrol at 37 degrees C for 15 min. This effect of diethylstilbestrol in decreasing the ATP content of mast cells correlated well with its inhibitory effect on histamine release. Diethylstilbestrol at 50 microM depleted the cells of ATP at 37 degrees C, but not at 0 degrees C, whereas [3H]diethylstilbestrol ( [monoethyl-3H]diethylstilbestrol) binding to rat mast cells was the same at 0 and 37 degrees C. It is concluded that diethylstilbestrol reduced the ATP content of rat mast cells by inhibiting metabolism of the cells, and consequently inhibited degranulation.
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PMID:Inhibitory effect of diethylstilbestrol on histamine release by rat mast cells and its relation to the cellular ATP content. 642 97

Growth and development of haematopoietic cells in vitro require the presence of specific regulatory molecules. Some of these molecular species appear to have a broad specificity, being able to promote the proliferation and differentiation of multipotential cells, as well as megakaryocytic, erythroid and granulocytic-progenitor cells. Such factors are present in medium conditioned by the growth of lectin-stimulated mouse spleen cells or WEHI-3 myelomonocytic leukaemia cells (WEHI-CM). Using WEHI-CM, we and other have been able to obtain permanently growing, non-leukaemic cell lines of a granulocytic or mast cell nature. Significantly, we have found that the factor in WEHI-CM necessary for the growth of these cells has co-purified with the multi-lineage stimulating activity present in WEHI-CM, suggesting that one molecule may be concerned in the development of multiple cell types. We have now used these cells to investigate the mode of action of this haematopoietic cell growth factor and have found that the requirement of this factor for survival and growth may lie in its ability to modulate ATP levels within the cells.
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PMID:Effect of haematopoietic cell growth factor on intracellular ATP levels. 685 7

An unusual type of posttranslational modification has been observed in a rat brain in vitro system. It consists in leucine addition to a preformed protein in such a way that the added leucine is not located at either the NH2 or the COOH terminus of the acceptor protein. The incorporation reaction requires ATP, ATP-generating components and tRNA. It is inhibited by aurintricarboxylic acid but does not require the presence of ribosomes or GTP. The incorporated leucine has a free NH2 group, and it is not released by leucine aminopeptidase or carboxypeptidase A. It is linked to the acceptor protein through a bond that is too alkali labile and too hydroxylamine labile to be a peptide bond. The simplest interpretation of the results consists in proposing that an ester bond is formed between the leucine and the side chain of a serine, threonine, or tyrosine in the acceptor protein.
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PMID:Transfer ribonucleic acid dependent but ribosome-independent leucine incorporation into rat brain protein. 717 78

Nitric oxide (NO.) plays a central role in the physiology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
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PMID:Nitric oxide in the gut. 758 76


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