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 amino acid sequence has been determined of a mouse mucosal mast cell protease isolated from the small intestines of mice infected with Trichinella spiralis. The active protease contains 226 residues. Those corresponding to the catalytic triad of the active site of mammalian serine proteases (His-57, Asp-102, and Ser-195 in chymotrypsin) occur in identical positions. A computer search for homology indicates 74.3% and 74.1% sequence identity of the mouse mast cell protease compared to those of rat mast cell proteases I and II (RMCP I and II), respectively. The six half-cystine residues in the mouse mast cell protease are located in the same positions as in the rat mast cell proteases, cathepsin G, and the lymphocyte proteases, suggesting that they all have identical disulfide bond arrangements. At physiological pH, the mouse and rat mucosal mast cell proteases have net charges of +3 and +4, respectively, as compared to +18 for the protease (RMCP I) from rat connective tissue mast cells. This observation is consistent with the difference in solubility between the mucosal and connective tissue mast cell proteases when the enzymes are extracted from their granules under physiological conditions.
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PMID:Amino acid sequence of a mouse mucosal mast cell protease. 270 64

The functional and biochemical characterization of rat bone marrow derived mast cells (RBMMC) confirms both species-related differences between rat and mouse bone marrow-derived mast cells (MBMMC) as well as mast cell heterogeneity in a single species. Such RBMMC have the staining characteristics of mucosal mast cells and contain the mucosal mast cell protease. The RBMMC release the preformed granule mediator beta-hexosaminidase both in response to immunologic stimulation with 200 ng Ag (net release 15.8 +/- 3.8%) and in response to 1 microM calcium ionophore A23187 (net release 21.8 +/- 6.8%). However, compound 48/80, substance P, and somatostatin did not induce mast cell degranulation. In experiments with optimal beta-hexosaminidase release, the RBMMC generated similar quantities of the newly formed arachidonic acid metabolites leukotriene C4 and PGD2 when stimulated with either Ag or calcium ionophore A23187. The RBMMC incorporate [35S]sulfate into proteoglycans consisting of 90% chondroitin sulfates and 10% heparin. The chondroitin sulfates were comprised of chondroitin 4 sulfate and chondroitin sulfate diB sulfated disaccharides in a ratio of 4/1. Although we show that RBMMC and MBMMC share a low histamine content, functional IgE receptors and unresponsiveness to cromolyn and selective secretagogues (compound 48/80, substance P, and somatostatin), we also provide evidence that RBMMC differ from MBMMC in their profile of newly generated mediators, preformed granule proteoglycan, and lack of proliferative response to mouse IL-3.
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PMID:Functional and biochemical characterization of rat bone marrow derived mast cells. 297 57

Rat peritoneal mast cell extract contains an activator of latent human granulocyte gelatinase. The activator has been partially purified and characterized. It shows a similarity to rat mast cell chymase in several properties including its molecular weight, substrate specificity and sensitivity to inhibitors. The activation of latent gelatinase with rat mast cell protease is dependent on protease concentration, incubation time and is mediated through the catalytic site of the activator. The significance of mast cell protease in the regulation of collagenolytic enzymes is discussed.
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PMID:Activation of latent human granulocyte gelatinase by rat mast cell protease. 302 42

We have isolated, cloned, and characterized cDNA and genomic DNA corresponding to the mRNA and gene for the rat mast cell protease, RMCP II. The amino acid sequence deduced from the cDNA provides evidence that this protease is synthesized as a precursor, with a signal peptide and additional residues at the N and C termini. RNA homologous to the cDNA is expressed only in mast cells. Analysis of RNA from the two subclasses of mast cell, mucosal and serosal, indicates subclass specific expression of the different proteases found in each of these two subclasses. S1 protection analysis and the sequence of the genomic clone indicate that the serosal mast cell protease, RMCP I, is likely to be coded for by a separate, highly homologous gene. A comparison of the exon/intron structure of the RMCP II gene with genes of related serine proteases further indicates that RMCP II is a member of a family of proteases distinct from those found in the pancreas. We have also isolated a third gene, highly homologous to RMCP II but different from it and from the gene for RMCP I. Analysis of the 5' transcriptional control region of both genes showed striking homology to the TATA box and enhancer regions of the pancreatic proteases.
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PMID:Cloning of the mast cell protease, RMCP II. Evidence for cell-specific expression and a multi-gene family. 354 19

Secretory granules of the rat basophilic leukemia (RBL-1) cell, a chemically generated tumor cell line maintained in tissue culture, were shown to stain with alcian blue but not with safranin counterstain and to have sparse, small, electron-dense granules. A Mr 25,000 protein was the major [3H]diisopropyl fluorophosphate-binding protein in extracts of RBL-1 cells. Double-immunodiffusion analysis of extracts revealed immunoreactivity for rat mast cell protease (RMCP)-II, a Mr 25,000 neutral protease present in the secretory granules of rat mucosal mast cells and cultured rat bone marrow-derived mast cells, but no immunoreactivity for RMCP-I, the predominant neutral protease of rat connective tissue mast cells. By radial immunodiffusion, there was 66.8 ng of RMCP-II per 10(6) cells. Whereas rat connective tissue mast cells stain with alcian blue and safranin and contain heparin proteoglycan, rat mucosal and rat bone marrow-derived mast cells stain with alcian blue only and contain a non-heparin proteoglycan and lesser amounts of histamine. Proliferation of rat mucosal mast cells in vivo and rat bone marrow-derived mast cells in vitro requires T-cell factors, whereas no comparable requirement has been observed for connective tissue mast cells. The transformed RBL-1 tumor cells, whose growth is independent of factors other than those present in standard tissue culture medium, has previously been shown to contain predominantly chondroitin sulfate di-B proteoglycans and low amounts of histamine. The similar histology and secretory granule biochemistry of the rat mucosal mast cells, rat culture-derived mast cell, and RBL-1 cell suggest that they comprise a single mast cell subclass distinct from the rat connective tissue mast cell.
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PMID:Homology of the rat basophilic leukemia cell and the rat mucosal mast cell. 392 82

The recovery of mast cells in adult rats after depletion induced by polymyxin-B has been studied. At days 17-18 after depletion the number of identifiable mast cells in the peritoneal fluid reached 3 X 10(6) cells/rat. Mast cell granule constituents such as histamine, heparin, mast cell protease and beta-glucuronidase increased steadily during the observation period, whereas the amount of N-acetyl-beta-glucosaminidase decreased during the first 2 weeks and was thereafter constant. At 2 weeks after depletion the peritoneal mast cells were biochemically restored. From 14 to 34 days (end of experimental period) cell growth occurred with a simultaneous accumulation of the various mast cell granule constituents.
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PMID:Mast cell restoration. A study of the rat peritoneal mast cells after depletion with polymyxin B. 626 1

The primary subsite specificities of human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II, bovine chymotrypsin A alpha, and the protease from strain V-8 of Staphylococcus aureus have been mapped with a series of tripeptide thiobenzyl ester substrates of the general formula Boc-Ala-Ala-AA-SBzl, where AA represents one of 13 amino acids. In addition, the effects of a P2 Pro and P4 methoxysuccinyl and succinyl groups were investigated. In an attempt to introduce specificity and/or reactivity into the substrate Boc-Ala-Ala-Leu-SBzl(X), the 4-chloro-, 4-nitro-, and 4-methoxythiobenzyl ester derivatives were studied. Enzymatic hydrolyses of the substrates were measured in the presence of 4,4'-dithiobis(pyridine) or 5,5'-dithiobis(2-nitrobenzoic acid), which provided a highly sensitive assay method for free thiol. The thio esters were excellent substrates for the enzymes tested, and in many cases, the best substrates reported here have kcat/KM values higher than those reported previously. The best substrate for human leukocyte elastase was Boc-Ala-Pro-Nva-SBzl(Cl), which has a kcat/KM of 130 X 10(6) M-1 s-1. A very reactive rat mast cell protease substrate, Boc-Ala-Ala-Leu-SBzl(NO2), was also found. The S. aureus V-8 protease was the most specific enzyme tested since it hydrolyzed only Boc-Ala-Ala-Glu-SBzl. Substituents on the thiobenzyl ester moiety of Boc-Ala-Ala-Leu-SBzl resulted in decreased KM values with human leukocyte elastase and rat mast cell protease I when compared to the unsubstituted derivative.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Active site mapping of the serine proteases human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II. Bovine chymotrypsin A alpha, and Staphylococcus aureus protease V-8 using tripeptide thiobenzyl ester substrates. 638 May 80

The activity of chymase was markedly inhibited by fatty acids with carbon chain lengths of 14-22 at doses greater than 0.02 microM, irrespective of the number of double bonds. Cis acids with a carbon chain length of 18, such as stearic acid, oleic acid, linoleic acid, and linolenic acid were potent inhibitors, whereas the trans isomer of oleic acid, elaidic acid, showed less inhibitory activity. The extent of inhibition by oleyl alcohol was almost the same as that by oleic acid, suggesting that the acid moiety itself was not necessary for the inhibition; but a fatty acid with a terminal functional amide, oleamide, showed little inhibitory activity. The inhibition was noncompetitive and was reversible, and the Ki value of oleic acid was 2.7 microM. Stearic acid and oleic acid inhibited all chymotrypsin-type serine endopeptidases tested. The ID50 values of these fatty acids for atypical mast cell protease were higher than those for the other chymotrypsin-type serine endopeptidases tested. Other proteases, such as papain, trypsin, collagenase, and carboxypeptidase A, except cathespin D, were not affected by stearic or oleic acid.
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PMID:Inhibition of chymase activity by long chain fatty acids. 642 74

The isolated chymotrypsin-like protease of rat mast cells was shown to cause an increase of vascular permeability in rat skin. Inactivation of the enzymatic activity of the cationic protease abolished the vasoactivity. The smallest effective dose of the maximally active enzyme was estimated to be 0.5 micrograms per injection site, which is less than the amount of the endogenous mast cell enzyme in areas of skin similar to that of an injection site. The smallest effective dose for bovine trypsin was similarly estimated to be 0.3 micrograms per injection site, which is in good agreement with the values previously reported by others. The results suggest that the mast cell protease may act as a mediator of inflammatory vasopermeability. The effect of the enzyme on two potential biological substrates was tested. The enzyme does not hydrolyze elastin, but degrades fibrin clot.
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PMID:The role of chymotrypsin-like protease of rat mast cells in inflammatory vasopermeability and fibrinolysis. 699 62

Following infection with the intestinal nematode Nippostrongylus brasiliensis, mucosal mast cell (MMC) proliferated in the jejunum and the peak of this response was associated with a nine-fold increase in the level of mucosal mast cell protease (RMCPII) in the mucosa. At this stage the protease constituted 10%-15% of the soluble protein from gut homogenates. Concomitant immunoperoxidase studies showed that during the early proliferation of the MMC, only a proportion of the cells in lamina propria and none of the MMC within the epithelium contained detectable RMCPII. Fourteen and 20 days post infection and following a secondary challenge, staining for RMCPII in lamina propria MMC was much stronger and a few intraepithelial mast cells also contained RMCPII. With time after infection an increasing proportion of intestinal goblet cells were specifically labelled, indicating an accumulation either of RMCPII or of an antigenically similar enzyme within mucous glycoproteins. The significance of the high levels of protease in parasitized gut and of its apparent cellular distribution is discussed in relation to the protective response against the parasite.
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PMID:Quantitative analysis of mucosal mast cell protease in the intestines of Nippostrongylus-infected rats. 704 82


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