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)

beta-Hexosaminidase, beta-glucuronidase, arylsulfatase, and tryptase were each released along with histamine from dispersed purified human lung mast cells of 40 to 80% purity by rabbit IgG anti-human IgE. The net per cent release ratio of each enzyme to histamine was determined over all doses of antibody employed to activate the mast cells and over all time points after activation, and indicated the per cent of each enzyme stored in secretory granules along with histamine. By multiplying the net per cent release ratio of each enzyme to histamine by total enzyme content in a preparation of 10(6) mast cells, values for secretory granule content per 10(6) mast cells were found to be 3.8 U for beta-hexosaminidase, 0.03 U for beta-glucuronidase, 0.03 U for arylsulfatase, and 0.9 U for tryptase. Subtype analysis of beta-hexosaminidase by diethylaminoethyl- (DEAE) cellulose chromatography revealed that the B isomer predominates in human mast cell secretory granules, whereas the A isomer predominates in secretory granules of the rat mast cell. Tryptase, the predominant neutral protease of the human mast cell secretory granule, has a m.w. of 130,000 by gel filtration chromatography, whereas the major neutral protease of the rat mast cell is chymotryptic and of 25,000 m.w. The presence of acid hydrolases, a tryptase, and histamine in human mast cell secretory granules suggests that the activated mast cell plays a direct role in the production of acute and subacute inflammation.
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PMID:Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. 700 36

Basophils and mast cells possess large metachromatically staining granules which contain sulfated glycosaminoglycans as well as vasoactive compounds. To determine whether these granules might also have lysosomal properties, we used electron microscopy and cytochemistry to localize arylsulfatase B in rat basophils and mast cells. In basophils of bone marrow, enzymatic reaction product was consistently seen in many, but not all, of the basophil granules. In some cells, the enzyme could also be demonstrated in the Golgi region, restricted to a single cisterna and small vesicles. It was never seen in rough endoplasmic reticulum (RER), although the paucity of cells made adequate sampling difficult. In mast cells of bone marrow and the peritoneal cavity, enzymatic reaction product was consistently found in some cytoplasmic granules of varying sizes and shapes where it characteristically rimmed the periphery of the granule just beneath the limiting membrane. It should be emphasized, however, that the majority of granules were not reactive. Reaction product could also be found occasionally in segments of RER, and in the Golgi region with a distribution similar to that of the basophil. The presence of lysosomal arylsulfatase in granules of developing basophils in bone marrow suggests that some basophil granules, like those of neutrophils, eosinophils, and monocytes are primary lysosomes. Some mast cell granules also contain this lysosomal enzyme, although it is not clear from the present data whether these granules are primary or secondary lysosomes.
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PMID:Cytochemical localization of arylsulfatase B in rat basophils and mast cells. 741 98

The growth of ovine and caprine mast cells in bone marrow cultures has been achieved using recombinant ovine interleukin-3 (rOvIL-3) and recombinant ovine stem cell factor (rOvSCF). After approximately 2-3 weeks' growth in optimal concentrations of either rOvIL-3 alone or a combination of rOvIL-3 and rOvSCF, the majority of the cells produced in bone marrow culture from both species were mast cells. The significant increase in the total numbers of cells and survival times of the cultures when both cytokines were present compared to either alone, indicated synergy between rOvIL-3 and rOvSCF on mast cell growth. Ovine and caprine cells cultured in rOvIL-3 alone produced a four-fold increase in cell numbers compared with medium only controls. The resulting cultures contained up to 52% mast cells by day 18 and had a lifespan of 3-4 weeks. In contrast, cells from both species grown in both rOvIL-3 and rOvSCF produced up to six times more cells than the equivalent rOvIL-3 stimulated cultures, contained up to 69% mast cells by day 21 and could be maintained for at least 6 weeks. Ovine cells grown in rOvIL-3 alone or rOvIL-3 and rOvSCF contained significantly more aryl-sulfatase and serine protease but similar amounts of beta-hexosaminidase compared with caprine cells during the second week of culture. There were no significant differences in the granule-associated mediator content of cells from either individual species grown in rOvIL-3 alone compared with those grown in rOvIL-3 and rOvSCF during the first 21 days of culture.
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PMID:The effects of recombinant ovine interleukin-3 and recombinant ovine stem cell factor on the growth and mediator expression of caprine and ovine bone marrow-derived mast cells. 953 70

Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, gamma-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HN-SO2-NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications.
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PMID:Therapeutic potential of sulfamides as enzyme inhibitors. 1671 Aug 59

The sulfamide moiety, similarly to the structurally related sulfonamide and sulfamate ones, is widely employed in medicinal chemistry for the design of biologically active compounds. Amongst the enzymes for which sulfamide-based inhibitors were designed are the carbonic anhydrases (CAs), and a large number of proteases belonging to the aspartic protease (HIV-1 protease, gamma-secretase), serine protease (elastase, chymase, tryptase and thrombin, among others) and metalloproteinase (carboxypeptidase A [CPA] and matrix metalloproteinase [MMP]) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays an important role in the binding of the inhibitor to the active site cavity. This is achieved either by directly coordinating to the metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or, as in the case of the cyclic sulfamides, acting as HIV protease inhibitors interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HN-SO(2)-NH motif that substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physicochemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability etc., due to the intrinsic properties of this highly polarised moiety when attached to an organic scaffold. This interesting motif is, thus, of great value for the design of pharmacological agents with many applications.
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PMID:The sulfamide motif in the design of enzyme inhibitors. 2014 8


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