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)

Two of the major enzymes present in and released from rat mast cells are chymotrypsin-type serine protease (chymase) and trypsin-type serine protease (tryptase), and these have been postulated to be important in the inflammatory reactions. There have been no clear data regarding the trypsin-type protease in rat mast cells. Tryptase was recently purified from rat peritoneal mast cells with an associated protein (trypstatin) that inhibited the protease activity above pH 7.5. Chymase was also purified from rat peritoneal cells by employing a one-step method involving hydrophobic chromatography on octyl-Sepharose 4B or arginine-Sepharose 4B. The properties of chymase and tryptase were described in relation to substrate specificity and their relative sensitivity to inhibitors. It was found that proteolytic activities of these enzymes were modulated by naturally occurring substances, such as phosphoglycerides, long-chain fatty acids, and trypstatin. There is as yet little evidence for the physiological roles of these enzymes in the inflammatory reaction. It has been found that the specific, low-molecular-weight inhibitor of chymase, chymostatin, and that of tryptase, leupeptin, inhibit histamine release induced by addition of anti-rat IgE to mast cells. However, the inhibitors with molecular weights of more than 6000 were found to have no effect in this process. The data suggest that chymase and tryptase in mast cell granules play a crucial or significant role in the process of degranulation.
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PMID:Chymotrypsin- and trypsin-type serine proteases in rat mast cells: properties and functions. 389 Jul 54

Proteases in preparations of carboxypeptidase A progressively inactivate solutions of the apoenzyme but not the metal-containing enzyme. Free amino acids generated by proteolysis interfere with spectral studies after reconstituting the apoenzyme with cobalt. Purification by affinity chromatography eliminates this effect. Affinity-purified apoenzyme is susceptible to digestion with chymotrypsin but the metalloenzyme is not.
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PMID:Protease susceptibility of zinc- and apo-carboxypeptidase A. 391 41

Chondroitin sulfate E proteoglycan was extracted in the presence of protease inhibitors from 6 X 10(9) mouse bone marrow-derived, interleukin 3-dependent mast cells, of which 3 X 10(7) had been biosynthetically labeled with [35S]sulfate or [3H]glycine. Chondroitin sulfate E proteoglycan was purified to apparent homogeneity by density-gradient centrifugation, differential molecular weight dialysis, DEAE-52 ion exchange chromatography, and Sepharose CL-4B gel filtration chromatography. Chondroitin sulfate E proteoglycan, radiolabeled with [3H]glycine or [35S]sulfate, filtered as a single peak of radioactivity on Sepharose CL-4B with a Kav of 0.41. When purified [3H]glycine-labeled proteoglycan was digested with chondroitinase ABC and subjected to gel filtration, all of the radioactivity was shifted to a lower molecular weight. As assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis the Mr of the peptide core obtained by chondroitinase ABC treatment was approximately 10,000. The purified proteoglycan was resistant to degradation by collagenase, clostripain, trypsin, chymotrypsin, elastase, chymopapain, V8 protease, proteinase K, and Pronase, as assessed by gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the core peptide of the intact proteoglycan revealed that glycine, serine, and glutamic acid/glutamine accounted for 70% of the total amino acids and were present in a molar ratio of 4.3/1.6/1.0. When analyzed for neutral hexose content by gas-liquid chromatography, the proteoglycan contained approximately 2% of its weight as mannose, fucose, galactose, and other sugars, indicating that oligosaccharides were linked to the peptide core. The mouse bone marrow-derived mast cell chondroitin sulfate E proteoglycan, like the rat serosal mast cell heparin proteoglycan, is markedly protease resistant, has highly sulfated glycosaminoglycans, and contains a peptide core that is rich in serine and glycine. These characteristics of the mast cell class of intracellular proteoglycans may contribute to their function in stimulus-induced granule secretion as well as in mediator storage, including retention of cationic neutral proteases.
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PMID:Purification and analysis of the core protein of the protease-resistant intracellular chondroitin sulfate E proteoglycan from the interleukin 3-dependent mouse mast cell. 393 50

Acid-acetone extracts of the chicken rectum were subjected to chromatographic and electrophoretic separation, and two new smooth muscle-contracting substances close to purity were obtained. One of them showed chemical and biological characteristics similar to those of substance P, but it was clearly different from substance P on the basis of chromatographic and electrophoretic criteria. Thus, one could be a peptide belonging to the substance P-family. The other substance was also shown to be of peptide nature since its biological activity was destroyed by chymotrypsin and carboxypeptidase A. Parallel bioassay on the two tissues of the longitudinal muscle of the guinea-pig ileum and the isolated whole chick rectum revealed that none of the peptides such as substance P, physalaemin, kassinin, eledoisin, bradykinin and angiotensin II could be a candidate for the active substance. The biological activity was not antagonized by naloxone, suggesting that the substance was a peptide other than the opioid compounds. The molecular sizes estimated by gel filtration are 1300 for the substance P-like peptide and 1600 for the other substance. The possible physiological roles of the two substances as an excitatory non-adrenergic, non-cholinergic transmitter were discussed.
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PMID:Isolation of smooth muscle excitatory substances from chicken rectum and their characterization. 395 45

Serine esterases were detected in the granules of mucosal mast cells from rat, mouse, sheep, and man. Successful demonstration of enzyme activity required brief fixation (6 h) of tissues in 4% paraformaldehyde. Staining with naphthol AS-D chloroacetate produced an intense red reaction product in intraepithelial mucosal mast cells (globule leucocytes) and mucosal mast cells within the lamina propria of the gastrointestinal tract. The mast cell identity of cells stained for esterase was confirmed by sequential staining with toluidine blue (pH 0.5). Furthermore, the numbers of cells detected after staining for esterases or with toluidine blue were highly correlated. Esterase activity within mucosal mast cells/globule leucocytes from all species was inhibited with the serine enzyme inhibitor phenylmethylsulphonyl fluoride. Further histochemical studies with the substrate, N-acetyl-DL-phenylalanine B-naphthyl ester, indicated that mucosal mast cells and globule leucocytes contain esterases which are chymotrypsin like in substrate specificity.
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PMID:Histochemical demonstration of chymotrypsin like serine esterases in mucosal mast cells in four species including man. 398 50

The complete amino acid sequence of beta-microseminoprotein of human seminal plasma was determined by automated Edman degradation of the protein and peptides which were obtained by enzymatic cleavage with trypsin, chymotrypsin and Staphylococcus aureus V8 proteinase. The carboxyl-terminal sequence of the protein was established with the aid of carboxypeptidase A. The amino acid sequence of this protein proved to be as follows: (sequence; see text) Thus, beta-microseminoprotein consisting of 93 amino acid residues has a molecular mass of 10 652 Da. The linear structure of this protein represents the first complete amino acid sequence of a sperm-coating protein specific to human seminal plasma.
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PMID:The amino acid sequence of human beta-microseminoprotein. 399 56

The ability of a number of p-nitrophenylethyl, alkyl phenylalkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the homocytotropic antibody-mediated release of histamine from rat peritoneal mast cells has been tested. The effectiveness of these same phosphonates against the activated first component of rat complement (C'1a) has also been investigated. The rat mast cell esterase activated by the reaction of antigen and homocytotropic antibody resembles chymotrypsin in its reactivity with the phenylalkyl and chloroalkyl phosphonate, but is unlike this protease in its greater responsiveness to the 5-aminopentyl phosphonate relative to the pentyl phosphonate. The antigen-homocytotropic antibody-activated mast cell esterase and chymotrypsin, thus, appear to be similar, but different enzymes; i.e., they are parazymes (see reference 4, p. 501). There are distinct differences in the pattern of inhibition given by the phenylalkyl and aminoalkyl and alkyl phosphonates of the homocytotropic antibody-mediated histamine release from rat peritoneal mast cells and from guinea pig lung slices. On the basis of these differences it is concluded that the esterases activated by the combination of antigen and homocytotropic antibody on the mast cells of the two species are not the same. The arithmetic dose response curve found for the action of the phosphonates on the antigen-induced histamine release from rat peritoneal mast cells contrasted sharply with the logarithmic relationship found when these same inhibitors acted on the guinea pig lung system. This suggests that in addition to the antigen-antibody-activated esterases being unlike, the detailed mode of histamine release from the mast cells of the guinea pig lung differs from that of the mast cells of the rat peritoneum. Distinct and large differences were found in the pattern of inhibition of histamine release from rat peritoneal mast cells and of rat C'1a given by the phenylalkyl, and chloroalkyl and alkyl phosphonates implying that esterase activated by the combination of antigen with the sensitized rat peritoneal mast cells is not C'1a. Thus, the results with the peritoneal mast cells lead to the same conclusion as the previous work with guinea pig lung slices; i.e., the antigen-antibody-activated esterase involved in the homocytotropic antibody-mediated release of histamine is not part of the complement system.
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PMID:Mechanisms of immunologic injury of rat peritoneal mast cells. I. The effect of phosphonate inhibitors on the homocytotropic antibody-mediated histamine release and the first component of rat complement. 416 85

It has been noted that from days 18 to 22 (birth) during the second intrauterine period of morphogenesis of the rat pancreas the accumulation of enzymes increases dramatically. We studied the effect of altered maternofetal blood flow on the development of the rat pancreas during the critical second period. Our studies indicate that during pancreatic cytodifferentiation, reduction in maternofetal blood flow not only reduces the weight of the pancreas (68% of control) and diminishes the total activities of enzymes but that the changes in specific activities of the enzymes do not appear to be coordinate. The specific activities of amylase decreased to 59,000 units from the control value of 103,000 units (P less than 0.01) and lipase decreased to 4000 units from a control value of 7350 units (P less than 0.001). In contrast, the specific activities of trypsin (ogen), chymotrypsin (ogen) and (pro)-carboxypeptidase A and B are not changed. These results suggest that reduction in maternofetal blood flow caused a selective decrease of fetal rat amylase and lipase during the third trimester of gestation.
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PMID:The effect of reduced maternofetal blood flow on the development of fetal pancreatic acinar cells and enzymes. 616 28

Stimulation of rat mast cell suspension from actively sensitized rats with antigen in vitro produced a parallel release of histamine and enzyme, probably proteolytic activity, which releases p-nitrophenol from an L-tyrosine-p-nitrophenyl ester derivative (TPNE). The histamine and enzyme release correlated with respect to their dependence on antigen concentration, reaction time and inhibition by 2,4-DNP and papaverine. In contrast, more than 50% of total histamine but nearly no enzyme was released by the ionophore A 23.187 and C 48/80 (each less than or equal to 1 microgram/ml). The enzyme was apparently secreted predominantly in a particular form. It was approximately 50% inactivated by heating for 1 h at 56 degree C or by incubation for 3 h at 37 degrees C with the chymotrypsin inactivator tosyl-phenylalanine chloromethylketone (TPCK; 2.5 X 10-4 M) or for 5 min at 37 degrees C with benzyl sulphonyl fluoride (2.5 X10-4 M), which reacts with SH groups. Heating for 3 min at 100 degrees C destroyed it completely. On the basis of these properties we suggest that the antigen released enzyme is the known granulabound chymase from rat mast cells. TPNE was not only a cleavable substrate for the enzymatic activity in the 800 g cell supernatant following antigen stimulation, but also a strong inhibitor of the histamine release on administration before antigen (IC50 approximately 10-6 M). It appears that the same enzyme activity acts initially intracellularly as activator of the histamine secretion and then is subsequently released along with histamine as a further mediator. Extracellularly this enzyme may act as a modulator of inflammatory reactions in type I allergy both locally and systemically.
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PMID:Selective antigen-stimulated release of proteolytic activity from rat mast cells. 616 86

Zymogen activation is an important biochemical control process and has important physiological and pathological implications. We have simultaneously measured both procarboxypeptidase A, the enzyme precursor, and carboxypeptidase A, its active product, in serum by using an affinity resin and the synthetic peptide substrate N-(2-furanacryloyl)-L-phenylalanyl-L-phenylalanine. Serum procarboxypeptidase A is activated by trypsin, chymotrypsin, plasmin, subtilisin, or urokinase but not by thrombin or enteropeptidase. The molecular weight of the precursor is approximately 5000-10 000 greater than that of the active product. Both enzyme and precursor increase in serum in the course of pancreatic inflammation, but the degree of activation can vary up to 2000-fold, independent of the amount of precursor present. The existence of this pancreatic proteolytic precursor in serum opens new avenues for the investigation of zymogen activation and its regulation.
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PMID:Human serum procarboxypeptidase A. 634 78


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