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)

The biogenic amines and heparin of rat peritoneal mast cells were labelled in vivo by the injection of amine precursors (3H-histidine and 3H-5-hydroxytryptophan) and 35S-sodium sulfate. Uptake of label was rapid, probably reflecting the synthesis of new granule material, but the elimination was slow. Half-lives of radiolabelled histamine (23 days) and 5-hydroxytryptamine (5-HT; 25 days) did not differ statistically from that of heparin (35 days). The slow elimination rates suggest that mast cell secretion is of little biological significance under normal conditions but are well compatible with the idea that mast cell function is related to secretion evoked by appropriate immunological stimuli. It further permitted an analysis of the amine storage by repeated injections of unlabelled 5-HT. A 15-fold increase in 5-HT content was obtained while the total amine content remained constant. The uptake of 5-HT was balanced by a reduction of histamine in a molar 1:1 ratio. A displacement of histamine by 5-HT was further indicated by increased elimination rate of radiolabelled histamine in response to 5-HT injections. The results support previous binding studies in vitro and indicate that histamine and 5-HT are bound to identical storage sites in the mast cell granules.
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PMID:Storage and turnover of histamine, 5-hydroxytryptamine and heparin in rat peritoneal mast cells in vivo. 682 30

Intact rat peritoneal mast cells were separated by elutriation into fractions differing in cell size, the smallest cells (less than 12 microns) exhibited high histamine synthetic activity (200-300 pmol of histidine decarboxylated per hr/10(6) cells) and contained little histamine (less than 2 pg/cell). With increasing cell size, histamine synthetic activity diminished to less than 20 pmol/hr/10(6) cells and histamine content increased to greater than 12 pg/mast cell. A gradation in histamine release in response to Compound 48/80 was also observed; small mast cells were resistant, those of intermediate size (12-13 microns diameter) were partially responsive and large mast cells (14-17 microns) were fully responsive to Compound 48/80. These changes were related to the state of maturity of the mast cells as indicated by their histochemical reactions to Alcian blue and safranin, which stain nonsulfated heparin precursors and heparin, respectively. Fractions of small mast cells were predominantly immature cells (70-85% of the cells were Stage I) with few granules, whereas fractions of large cells contained mostly mature cells (greater than 80% Stages III and IV) with numerous heparin-containing granules. Fractions in between contained mast cells at intermediate stages (Stages II and III) of development. Degenerative changes, namely decreased viability and diminished responsiveness to Compound 48/80, were evident, however, in fractions of the largest cells (greater than 17 microns). This and other work indicate that, even in adult rats, peritoneal mast cells are heterogeneous and can be separated on the basis of size into subpopulations that differ markedly in histamine content, histamine synthetic activity and ability to release histamine in response to Compound 48/80.
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PMID:Changes in histamine synthetic activity, histamine content and responsiveness to compound 48/80 with maturation of rat peritoneal mast cells. 682 84

Preincubation with (S)-alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, was found to markedly reduce, but not eliminate, the uptake of [3H]histidine by rat peritoneal mast cells. The Vmax for histidine transport for cells in which decarboxylation of histidine had been completely inhibited was 11.9 pmoles per min per 10(6) cells, compared to a Vmax of 18.9 pmoles per min per 10(6) cells in the presence of active mast cell histidine decarboxylase. The Km of uptake was 139 microM in the presence of alpha-fluoromethylhistidine, several times higher than the Km of 44.0 microM in the uninhibited cell. alpha-Fluoromethylhistidine did not inhibit mast cell uptake of phenylalanine, a competitive inhibitor of histidine uptake but not a substrate for histidine decarboxylase; nor did it inhibit the uptake of histidine by non-mast cells, which lack histidine decarboxylase. Levels of intracellular [3H]histidine in mast cells were similar in the presence and absence of the decarboxylase inhibitor. Based on these observations, we propose that intracellular decarboxylation of histidine in the mast cell serves to specifically enhance the uptake of histidine by the relatively non-specific amino acid transporter present in the plasma membrane of the cell.
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PMID:Histidine uptake by isolated rat peritoneal mast cells. Effect of inhibition of histidine decarboxylase by alpha-fluoromethylhistidine. 683 Jun 20

4-Dimethylaminophenol, after i.v. injection, rapidly forms ferrihemoglobin and has been successfully used in the treatment of cyanide poisoning. The catalytic ferrihemoglobin formation is terminated by thioether formation of oxidized 4-dimethylaminophenol with reduced glutathione or cysteine 93 beta of hemoglobin. Hereby the physiological functions of human hemoglobin are markedly altered. After binding of two molecules of 4-dimethylaminophenol to tetrameric hemoglobin, the rate of autoxidation is increased about 6-fold. The oxygen affinity is 10 times higher than normal, the Hill coefficient is diminished nearly to unity, and the Bohr effect is reduced by about 50%. The physiologically important allosteric regulation of the oxygen affinity by 2,3-diphosphoglycerate is abolished, and the binding of 2,3-diphosphoglycerate to deoxyhemoglobin no longer functions. By molecular sieving, two alkylated hemoglobins were separated: a hemoglobin fraction with an unchanged low tetramer dimer dissociation, normal electronic spectra, and normal digestibility by carboxypeptidase A; and a second fraction with a high degree of dissociation, altered electronic spectra, and impaired digestibility. A tryptic peptide was isolated containing cysteine 93 beta and histidine 146 beta cross-linked by an arylic compound missing the dimethylamine label. The following reaction mechanism is concluded: Oxy-hemoglobin catalyzes the oxidation of 4-dimethylaminophenol, and the oxidation product, presumably N,N-dimethylquinonimine, is bound covalently to cysteine 93 beta by a thioether linkage. This adduct is unstable and autoxidizes further with the liberation of dimethylamine. The resulting quinoid thioether electrophilically attacks the COOH-terminal histidine of the beta-chain, thereby forming an intramolecular cross-link. By this latter reaction, hemoglobin lacks allosteric transition upon ligation and is obviously frozen in its quaternary R-state.
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PMID:Site and mechanism of covalent binding of 4-dimethylaminophenol to human hemoglobin, and its implications to the functional properties. 688 71

Equilibrium sedimentation experiments of the native acid phosphatase indicate a dimer-tetramer dissociating nonequilibrating system with a dimer Mr = 180,000 g/mol. The hydrolysis of nitrophenylphosphate was used to determine the sedimentation coefficient of the active species. The s20,w value for the species which degrades nitrophenylphosphate is 13.52 +/- 0.46 S in 1% sucrose and 13.72 +/- 0.11 S in 1.3 M sodium chloride, corresponding to the Svedberg value of the tetramer species. Several lines of evidence are presented which, together with previous data, indicate that the Schizosaccharomyces pombe nonspecific acid phosphatase is composed of 4 identical or nearly identical polypeptide chains: a, equilibrium sedimentation analysis of the enzyme in denaturing agents indicates the presence of homogeneous material having Mr = 90,800 g/mol; b, digestion with carboxypeptidase A releases 0.82 mol of tyrosine/monomer molecular weight. Concomitant phosphatase inactivation occurred during the splitting off of the tyrosyl terminal residue. Furthermore, a unique NH2-terminal residue (histidine) was determined.
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PMID:Molecular properties and active form of nonspecific acid phosphatase from Schizosaccharomyces pombe. 721 63

Carboxypeptidase A gamma from porcine pancreas was purified to homogeneity by ammonium sulfate fractionation, autolysis, batch absorption and elution from DEAF-Sephadex, and crystallization. The overall purification was about 32-fold with a yield of 31% and the specific activity of the purified protein was 108 units/mg protein. The apparent relative molecular mass determined by gel filtration on a Sephadex G-200 column was 38 900. The amino-terminal sequence of the porcine carboxypeptidase A gamma was Asn-Tyr-Ala-Thr-Tyr-His-Thr-Leu-Glu-Glu-Ile-Tyr-Asp-Phe-Met-Asp-Ile-Leu-Val-Ala -Glu-His-Pro-Gln-Leu- which was highly homologous to that of bovine carboxypeptidase A gamma. The purified enzyme was characterized with respect to isoelectric point (4.3). Km for N alpha-carbobenzoxyglycyl-L-phenylalanine (Cbz-Gly-LPhe) (20 mM), amino acid composition, pH optimum, pH stability, stability at different temperatures and effect of drying. The enzyme contained 1.01 mol zinc/mol and was inhibited by chelating agents such as EDTA and o-phenanthroline. Among substrates such as Cbz-Gly-LPhe, N alpha-benzoylglycyl-L-arginine, various kinds of amino acid esters, casein and elastin, porcine carboxypeptidase A gamma showed an enzymatic activity only towards Cbz-Gly-LPhe and casein. These data are in good agreement with the substrate specificity of bovine carboxypeptidase A.
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PMID:Crystallization and properties of carboxypeptidase A gamma from porcine pancreas. 727 15

The synthesis of the mast cell-degranulating peptide by liquid-phase fragment condensation is described. After the carboxyterminal of the peptide is condensated with polyethylene-glycol (Mr 10000) the following fragments are coupled stepwise on the polymer, a soluble carrier in dichloromethane by the dicyclohexylcarbodiimide/hydroxybenzotriazole-method. Pos. 17-21 Boc-Lys(Z)-Ile-Cys(SiPr)-Gly-Lys(Z) (I) Pos. 12-16 Boc-Pro-His(Trt)-Ile-Cys(Trt)-Arg(Tos) (II) Pos. 8-11 Boc-His(Trt)-Val-Ile-Lys(Z) (III) Pos. 5-7 Boc-Cys(SiPr)-Lys(Z)-Arg(Tos) (IV) Pos. 1-4 Boc-Ile-Lys(Z)-Cys(Trt)-Asn(Mbh) (V) It is practical to crystallize the polyethyleneglycol peptide-coupling products from ethanol after each step. Most of the protecting groups can be removed by treatment of the complete polyethylene-glycol-peptide in trifluoroacetic acid/HBr. In methanol, saturated with ammonia, the peptide is removed in the amid-form from the carrier. The guanidyl-blocking group disappears by solving the peptide in liquid HF. The crude peptide is converted into the tetra-S-sulfonate derivate by oxidative sulfitolysis and purified by ion-exchange and gel chromatography. After reduction by mercaptoethanol a cautious air-reoxidation of the SH- to the SS-peptide followed. Rechromatography on ion-exchange and dextran gels yields a peptide with good biological activity in rat cell histamin-liberation and inflammation inhibition compared with the natural recombinated product.
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PMID:[Basic peptides from bee venom, IV. Synthesis of the mast cell-degranulating peptide by liquid-phase fragment condensation (author's transl)]. 738 Mar 91

Glutaurine produces rapid and intensive degranulation of mast cells without affecting the composition of their granules. The mast cells of the individual organs differ in the type and extent of degranulation. There is a wide scale between excessive degranulation (mast cells of subcutaneous connective tissue and of the peritoneum), and unresponsiveness (mast cells of thyroid and lymph nodes), and there are also differences in time. The peritoneal mast cells stain positively with safranin, swell excessively and assume bizarre forms in response to 5 micrograms/rat glutaurine intraperitoneally. Frequent occurrence of lymphocyte-mast cell contacts seems typical. Glutaurine increases 3H-histidine uptake of the peritoneal fluid cells in general and 35S sulphate incorporation in the peritoneal mast cells in particular. Accumulation of these substances is more marked at 1 hour than at 3 hours after application.
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PMID:Complex morphological study of the effect of glutaurine in mast cells. 744 20

Tropomyosin (TM) has been isolated from the cardiac muscle, and fast and slow trunk (myotomal) muscles of the mature salmonid fish Atlantic salmon (Salmo salar) and rainbow trout (Salmo gairdneri). When examined electrophoretically, isoforms of TM were detected which were specific, and exclusive, to each type of muscle. Cardiac and fast muscles contained single and distinct isoforms, while slow muscle contained two distinct isoforms, closely related in terms of apparent M(r), and pI. There was no detectable difference between the same TM type from either salmon or trout. On a variety of gel systems, the cardiac and slow isoforms migrated in close proximity to each other and to rabbit alpha-TM. The fast isoform comigrated with rabbit beta-TM. In developing salmon fry, a more acidic (unphosphorylated) variant of TM was present in addition to, and of similar M(r) to, the fast adult isoform. This TM declined in steady-state level during maturation and was virtually undetected in adult muscle. All of the isolated TMs contained little or no covalently bound phosphate and were blocked at the N-terminus. The amino acids released by carboxypeptidase A, when ordered to give maximal similarity to other muscle TMs, were consistent with the following sequences: fast (LDNALNDMTSI) and cardiac (LDHALNDMTSL). The C-terminal region of the slow TM contained His but was heterogeneous. In viscosity measurements, performed as a function of increasing protein concentration, at low ionic strength (t = 5 degrees C, pH 7.00), fast TM exhibited the highest relative viscosity values. Lower and equivalent levels of polymerisation occurred with the cardiac and slow TMs. Polymerisation of all three isoforms was temperature-dependent, with cardiac TM being least sensitive and fast TM being most sensitive. Determination of the complete coding sequence of adult fast TM confirmed the findings of the carboxypeptidase analysis, but the remainder of the sequence more closely resembled alpha-type TMs than beta-type TMs. Overall, salmon fast TM contains 20 (mostly conservative) substitutions compared to rabbit striated muscle alpha-TM and 40 (mostly conservative) substitutions compared to rabbit striated muscle beta-TM. This demonstrates that electrophoretic mobility is not, in all instances, a suitable method to assess the isomorphic nature of striated muscle TMs.
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PMID:Characterisation of fast, slow and cardiac muscle tropomyosins from salmonid fish. 755 55

In an effort to identify genes that are differentially regulated during mast cell development, subtracted cDNA prepared from wild-type murine P815 mastocytoma cells and a P815 subline that exhibits properties of mast cell differentiation was used to screen mast cell cDNA libraries. Several known mast cell-specific cDNAs were isolated including mast cell carboxypeptidase A (MC-CPA), murine mast cell protease-5 (MMCP-5), and gp49. A novel cDNA, designated Tbc1, was identified that showed differential expression in the two mast cell lines. The amino acid sequence predicted from the cDNA contains a 200 amino acid domain that is homologous to regions in the tre-2 oncogene and the yeast regulators of mitosis, BUB2 and cdc16. The N-terminal region contains a number of cysteine and histidine residues, potentially encoding a zinc finger domain. Tbc1 is a nuclear protein and is expressed in highest levels in hematopoietic cells, testis and kidney. Within these tissues, expression of Tbc1 is cell- and stage-specific. Based on sequence similarity, pattern of expression and subcellular localization, Tbc1 may play a role in the cell cycle and differentiation of various tissues.
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PMID:Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16. 756 74


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