Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lectins from Ricinus communis and Glycine max, as well as wheat germ agglutinin and concanavalin A, caused a dose-dependent release of histamine from mast cells present in the mixed peritoneal cells from the rat. In addition, histamine release in an IgE-mediated and a compound 48/80-mediated reaction was inhibited in cells which had been pretreated with these lectins. With concanavalin A and the R. communis lectin both effect were prevented by the addition of the appropriate monosaccharides to the incubations. However, the lectin-induced histamine release and the lectin-induced inhibition of subsequent IgE-mediated histamine release could be dissociated: thus L-rhamnose, a hexose not ordinarily found on mammalian cell membranes, a specifically inhibited histamine release which was caused by the lectin from R. communis without affecting the inhibition of IgE-mediated histamine release. Conversely, D-fucose, which also is not a constituent of cell membrane glycolipids or glycoproteins prevented the inhibition of IgE-mediated histamine release by this lectin without affecting the lectin-induced histamine release. Furthermore, the nominally galactose-specific lectins from Sophora japonica and Ulex europeus inhibited IgE-mediated histamine release while causing little if any histamine release themselves. High concentrations of the lectin from Lotus tetragonolobus failed to cause histamine release or to affect the IgE-mediated histamine release reaction. Based on the known structural specificity of these lectins and the amounts of the lectins which were required to demonstrate an effect, it was concluded that D-galactose, alpha-linked, intrachain D-glucose (or mannose), and N-acetylglucosamine residues but probably not N-acetyl-galactosamine or L-fucose residues in the glycolipids or glycoproteins of the mast cell membrane can play a role in the initiation of histamine release and in the desensitization of the cells to subsequent histamine release-inducing stimuli.
 ...
PMID:Inhibition of IgE and compound 48/80-induced histamine release by lectins. 5 Oct 3

Angiotensin-converting enzyme has been solubilized from a particulate fraction of rabbit lung and purified to apparent homogeneity in 11% yield by a procedure including fractionation with DEAE-cellulose and calcium phosphate gel, elution from Sephadex G-200, and lectin affinity chromatography. The molecular weight estimated by equilibrium sedimentation was approximately 129,000, either in the absence or presence of 6 M guanidine hydrochloride. A slightly higher value of 140,000 determined for the reduced, denatured protein by gel electrophoresis in the presence of sodium dodecyl sulfate and a much higher figure derived from gel filtration are probably due to the glycoprotein nature of the enzyme. Its oligosaccharide content accounted for 26% of the weight calculated from its amino acid and carbohydrate composition. The estimated content of sugar residues per mole was: galactose, 57; N-acetylglucosamine, 53; mannose, 43; N-acetylneuraminic acid, 19; and fucose, 4. Threonine and alanine were identified, respectively, as NH2-terminal and COOH-terminal residues by the dansylation procedure and by digestion with carboxypeptidase A. The enzyme was found to contain approximately 1 g atom of zinc per mol. Km values for hydrolysis of hippurylhistidylleucine and angiotensin I were 2.3 and 0.07 mM, and the corresponding turnover numbers were 15,430 and 792 mol/min/mol at 37 degrees. Bradykinin was also a substrate, and release of its COOH-terminal dipeptide, Phe-Arg, was catalyzed at a comparable rate to that of His-Leu from the COOH terminus of angiotensin I. Enzyme activity required the presence of chloride ions and was inhibited by EDTA and by low concentrations of Bothrops bradykinin-potentiating peptides. In addition, hydrolysis of hippurylhistidylleucine was inhibited competitively by other defined peptides, including di- and tripeptides, which were not substrates.
 ...
PMID:Pulmonary angiotensin-converting enzyme. Structural and catalytic properties. 16 57

A solitary mastocytoma of the skin was investigated to assess the lectin-binding pattern of human mast cells. Of 18 Fluorescein-labelled lectins tested, nine reacted with mast cell granules. While lectins recognizing N-acetylgalactosamine or fucose residues did not stain mast cells, lectins with binding sites for N-acetylglucosamine, alpha-methyl mannopyranoside, galactose, complex carbohydrates of N-acetyl-lactosamine type and sialic acid gave a positive reaction.
 ...
PMID:Lectin-binding studies of a human skin mastocytoma. 274 58

Chrysotile asbestos interacts with mucin-secreting cells of tracheal organ cultures, causing an increase in secretion of mucin into the culture medium. This response occurs in the absence of obvious morphologic damage to tracheal epithelial cells. We speculated that asbestos-induced hypersecretion was regulated by the interaction of fibers with specific carbohydrate residues on the cell surface. To test this hypothesis, lectins, i.e., proteins with a high affinity for mono- and oligosaccharides on the plasma membrane, were added to tissues 30 min before addition of chrysotile. Secretion of mucin into the medium was then determined over a 2-hr period by using incorporation of 3H-glucosamine. Blocking of alpha-D-mannose and alpha-D-glucose residues inhibited chrysotile-induced hypersecretion (p less than 0.05), whereas lectins blocking residues of alpha-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, alpha-L-fucose and sialic acids were ineffective. Preincubation of cultures with carboxypeptidase A or phospholipase A2, but not with neuraminidase, diminished mucin secretion caused by chrysotile. To determine if the positive surface charge of chrysotile was important in interaction with mucin cells, we examined comparatively the effects of various polycations (cationic ferritin, polylysine, DEAE-dextran) and chrysotile after leaching of fibers to remove Mg2+. Although use of polycations enhanced secretion of mucin, effects were not as striking as those observed with chrysotile. In contrast, leached chrysotile failed to elicit a hypersecretory response. These results suggest the interaction of a positively charged component (presumably Mg2+) of chrysotile with glycolipids and glycoproteins containing terminal residues of alpha-D-mannose or alpha-D-glucose.
 ...
PMID:Studies using lectins to determine mineral interactions with cellular membranes. 631 63

The N-acetyl glucosamine (GlcNAc)-specific lectin Datura stramonium agglutinin (DSA) rapidly and sugar-specifically released histamine from rat peritoneal mast cells, and pertussis toxin (IAP) inhibited it, suggesting that DSA activated mast cells via an IAP-sensitive G protein pathway. The additive effects of DSA and basic secretagogues such as compound 48/80 that activate IAP-sensitive G protein directly suggest that they shared the same mechanism of action including involvement of the IAP-sensitive G protein. Using lectin-blotting, blots of the corresponding glycoproteins detected by DSA diminished by haptenic sugar or pretreatment of the cells with N-glycosidase F, suggesting that the binding of DSA was responsible for the mast cell activation. The other GlcNAc-specific lectins such as Phytolacca americana mitogen, Solanum tuberosum agglutinin and wheat germ agglutinin (WGA) inhibited the histamine release induced by DSA, suggesting that these lectins were antagonists, but DSA was an agonist. Sialic acid-specific Macckia amurensis mitogen (MAM) inhibited the histamine release, and neuraminidase-treatment decreased mast cell activation induced by DSA. At least four mast cell glycoproteins that have affinity to DSA, WGA and MAM and are sensitive to neuraminidase-treatment were detected by lectin-blotting. Some of them may be binding sites coupled to histamine release including the IAP-sensitive G protein pathway. DSA is a useful tool for studying signal transduction of mast cells including the involvement of the IAP-sensitive G protein.
 ...
PMID:Datura stramonium agglutinin released histamine from rat peritoneal mast cells that was inhibited by pertussis toxin, haptenic sugar and N-acetylglucosamine-specific lectins: involvement of glycoproteins with N-acetylglucosamine residues. 753 33

A confocal fluorescence microscope using fluo-3 and 9-(dicyanovinyl)- julolidine (DCVJ) was used to study the mast cell activation by the N-acetyl glucosamine oligomer specific lectin Datura stramonium agglutinin (DSA) and inhibition by antagonist lectins having affinity to N-acetyl glucosamine (GlcNAc). DSA induced a transient increase in intracellular free calcium concentration ([Ca2+]i) followed by cytoskeletal disassembly and reassembly in rat peritoneal mast cells. These changes induced by DSA resulted in histamine release. The time course of fluorescence intensity in mast cells loaded with fluo-3- or DCVJ and activated by DSA resembled those activated by the basic polymer compound 48/80. Inhibition of [Ca2+]i rise by antagonist lectins was responsible for the inhibition of cytoskeletal assembly and the consequent histamine release induced by DSA. At the level of the individual cell, a mast cell stimulated by DSA responds in an all-or-none fashion. DSA possible induced intracellular calcium mobilization and cytoskeletal change by recognizing the GlcNAc-oligomer residues of specific glycoproteins of mast cells.
 ...
PMID:An initial signal of activation of rat peritoneal mast cells stimulated by Datura stramonium agglutinin: a confocal fluorescence microscopic analysis of intracellular calcium ion and cytoskeletal assembly. 753 34

1. Polyethylenimine with a molecular weight of 600 (PEI6) was the simplest and the most useful to investigate mast cell-activating mechanisms via pertussis toxin (IAP)-sensitive G protein pathway. 2. IAP, lidocaine, or dibutyryl cyclic AMP were inhibitors of the histamine release induced by PEI6, but anti-allergic drug DSCG, the calcium antagonist, D-600, kinase inhibitors, H-7 and K252a, or the calmodulin inhibitor, W-7 were not. 3. The additive effects of compound 48/80 and PEI6 suggested that the action sites for PEI6 overlapped the binding sites of compound 48/80. 4. Mast cell activation induced by PEI6 was sugar-specifically inhibited by N-acetylglucosamine(Glc-NAc)-specific lectins and/or by sialic acid (Sia)-specific lectins, suggesting that the action sites for PEI6 were glycoproteins having GlcNAc and/or Sia residues. 5. Four glycoproteins seemed to be involved in histamine release, including the IAP-sensitive G-protein pathway.
 ...
PMID:PEI6, a new basic secretagogue in rat peritoneal mast cells: characteristics of polyethylenimine PEI6 resemble those of compound 48/80. 759 Jan 4

It is difficult to isolate and impossible to propagate human mast cells in tissue culture. As an alternative to the use of human differentiated mast cells, a human leukaemic mast cell line (HMC-1), which can be propagated in vitro, has been employed in a number of studies. Carbohydrate binding proteins, lectins, have been used to characterise the terminal sugar residues of human mast cells in situ. The aim of the present study is to characterise the lectin binding sites of HMC-1 cells transplanted into severe combined immunodeficient (scid) mice. Lectins specific for the complex carbohydrates, neuraminic acid and N-acetylglucosamine residues showed generally a strong uniform binding pattern, whereas mannose and glucose specific yielded lectins a greater heterogeneity. This glycotope expression pattern has some similarities with those of human mast cells in situ, and therefore HMC-1 cells grown in scid mice constitute a valuable model system for the study of carbohydrate expression in human mast cells.
 ...
PMID:Lectin histochemistry of human leukaemic mast cells (HMC-1) transplanted into severe combined immunodeficient (scid) mice. 954 77

UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) catalyzes the second step in the biosynthesis of lipid A, a unique amphiphilic molecule found in the outer membranes of virtually all Gram-negative bacteria. Since lipid A biosynthesis is required for bacterial growth, inhibitors of LpxC have potential utility as antibiotics. The enzymes of lipid A biosynthesis, including LpxC, are encoded by single copy genes in all sequenced Gram-negative genomes. We have now cloned, overexpressed, and purified LpxC from the hyperthermophile Aquifex aeolicus. This heat-stable LpxC variant (the most divergent of all known LpxCs) displays 32% identity and 51% similarity over 277 amino acid residues out of the 305 in Escherichia coli LpxC. Although A. aeolicus LpxC deacetylates the substrate UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine at a rate comparable with E. coli LpxC, a phenyloxazoline-based hydroxamate that inhibits E. coli LpxC with K(i) of approximately 50 nM (Onishi, H. R., Pelak, B. A., Gerckens, L. S., Silver, L. L., Kahan, F. M., Chen, M. H., Patchett, A. A., Galloway, S. M., Hyland, S. A., Anderson, M. S., and Raetz, C. R. H. (1996) Science 274, 980-982) does not inhibit A. aeolicus LpxC. To determine whether or not broad-spectrum deacetylase inhibitors can be found, we have designed a new class of hydroxamate-containing inhibitors of LpxC, starting with the structure of the physiological substrate. Several of these compounds inhibit both E. coli and A. aeolicus LpxC at similar concentrations. We have also identified a phosphinate-containing substrate analog that inhibits both E. coli and A. aeolicus LpxC, suggesting that the LpxC reaction proceeds by a mechanism similar to that described for other zinc metalloamidases, like carboxypeptidase A and thermolysin. The differences between the phenyloxazoline and the substrate-based LpxC inhibitors might be exploited for developing novel antibiotics targeted either against some or all Gram-negative strains. We suggest that LpxC inhibitors with antibacterial activity be termed "deacetylins."
 ...
PMID:Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria. Inhibition of diverse UDP-3-O-(r-3-hydroxymyristoyl)-n-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs. 1075 2

A new sea urchin lectin from Toxopneustes pileolus, is D(+)galactose (Gal)-, D(+)fucose (Fuc)-specific. Incubation of rat peritoneal mast cells with the lectin in the presence of 0.3 mM CaCl2 for 10 min significantly and dose-dependently inhibited the histamine release induced by N-acetyl glucosamine (GlcNAc)-specific Datura stramonium agglutinin (DSA), an activator of the Gi-protein-dependent pathway in mast cells. This inhibition by the sea urchin lectin was sugar-specifically reversed in the presence of D(+)Gal or D(+)Fuc but not L(-)Fuc. The sea urchin lectin had no effect on the histamine release induced by compound 48/80, slightly inhibited the histamine release induced by substance P and mastoparan, and slightly enhanced the histamine release induced by melittin, but these effects were not dose-dependent. Compound 48/80, substance P, mastoparan and melittin are mast cell activators without sugar residues. It is suggested that the lectin binds to D(+)Gal residues of DSA to interfere with mast cell activation induced by DSA, a glycoprotein with arabinose and Gal residues. The effects of plant lectins with affinity to D(+)Gal, N-acetyl galactosamine and/or sialic acid and L(-)Fuc on the histamine release induced by DSA, compound 48/80 and substance P were also examined.
 ...
PMID:D-galactose-specific sea urchin lectin sugar-specifically inhibited histamine release induced by datura stramonium agglutinin: differences between sugar-specific effects of sea urchin lectin and those of D-galactose- or L-fucose-specific plant lectins. 1138 49


1 2 Next >>