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)

Histamine is released from isolated mast cell granules with intact membranes by calcium (10 mM) in presence of phosphatidyl serine (25-50 micrograms/ml). The release occurs both in Krebs-Ringer solution and in sucrose solution without monovalent cations, but the release in Krebs-Ringer solution is somewhat higher. The histamine release is associated with increased calcium uptake. But calcium is taken up much faster, within 5 sec, while it takes several minutes before histamine release is completed. The observations suggest a rapid uptake of calcium to the granule membrane, from which it may be more slowly released to the matrix, displacing histamine from its binding sites. Phosphatidyl serine with calcium could also conceivably change the membrane permeability causing increased influx of sodium ions, thus accounting for the mild enhancement of the release in Krebs-Ringer solution.
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PMID:Mechanism of histamine release from isolated mast cell granules by calcium with phosphatidyl serine. 619 40

To study the inflammatory properties of lysophosphatidylserine (a phospholipid acting as a histamine releaser), rats were subjected to local treatment with this compound. In the paw a rapid and dose-dependent edematous reaction occurred within 30-60 min (ED50 2.5 micrograms/rat). The effect was dependent on the intact configuration of serine head group since lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidic acid and N-acetimidyl-lysophosphatidylserine were uneffective. Indomethacin produced a weak inhibition but chlorpheniramine and cyproheptadine inhibited 50 and 70%, respectively. Consistently, the histamine stores of the paw were found to be decreased at the end of the lysophosphatidylserine effect. Increase in vascular permeability was observed also after the injection of lysophosphatidylserine into the dorsal skin and pleural cavity although the phospholipid was less effective in these regions. The fluid extravasation in the pleural cavity was 75% prevented by cyproheptadine. Parallel in vitro experiments showed that the effect of lysophosphatidylserine on isolated pleural and peritoneal mast cells is increased when a leukocyte lysate was also added. After centrifugation the activity was retained in the insoluble fraction. It is concluded that lysophosphatidylserine, injected locally, elicits an inflammatory reaction mediated by the components of mast cell granulus. The response may be amplified by the migration of other inflammatory cells into the exudate.
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PMID:Local effects of lysophosphatidylserine in rats. 620 95

Lysophosphatidylserine is a specific inducer of histamine release in isolated mast cells. To determine whether a similar effect is manifest in vivo, the phospholipid was injected (1-5 mg/kg i.v.) into mice and rats. A dose-dependent rise in blood histamine was observed in both animals. The several-fold increase in blood histamine occurred in the first minutes and was followed by a slower decline toward normal values. A second dose of lysophosphatidylserine was without effect. Systemic manifestations (depression, hypothermia, hypotension) were associated with the increased blood histamine level. When the tissue histamine stores accessible to lysophosphatidylserine were previously decreased by repeated phospholipid injections, no systemic symptoms occurred. Mobilization of carbohydrate reserves was also manifest during the action of lysophosphatidylserine. Prior treatment with compound 48/80 induced sustained refractoriness to lysophosphatidylserine. Structure-activity relationship demonstrated that the property to induce histamine release was linked to the structure of serine head group. Thus, other natural phospholipids or lysophospholipids were inactive. It is concluded that in analogy with the effect seen in vitro lysophosphatidylserine produces in vivo release of mast cell histamine.
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PMID:Lysophosphatidylserine as histamine releaser in mice and rats. 620 97

Penicillinase from Bacillus cereus 569/H was purified to homogeneity. Its active site was probed by use of an affinity label generated in situ by the diazotization of 6-aminopenicillanic acid, a catalytically poor substrate for this enzyme. The loss of activity arising during the inactivation is dependent upon pH and the penicillin:sodium nitrite ratio used. Optimal inactivation was obtained at pH 4.7 and reactivation could be prevented if subsequent purification and manipulations were performed at low pH. Inactivation by diazotized 6-aminopenicillanic acid was characterized further by tryptic and chymotryptic digestion of the inactivated enzyme and peptide mapping of the resulting digests. Amino acid analysis of the chymotryptic labeled peptide yielded a composition which corresponds to residues 41-46 (Ala-Phe-Ala-Ser-Thr-Tyr) in the published partial sequence of the enzyme (Thatcher, D. (1975) Biochem. J. 147, 313-326). Further digestion of this chymotryptic peptide with carboxypeptidase A reveals that serine-44 is modified in this affinity labeling procedure. Mass spectral analysis of the modified serine residue and alkali-released label, and comparison with spectra of model compounds indicates that the inactivation occurs with rearrangement of the beta-lactamthiazolidine structure to a dihydrothiazine.
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PMID:Bacillus cereus 569/H penicillinase serine-44 acylation by diazotized 6-aminopenicillanic acid. 630 23

Up to 43% of the viable bacteria from the rumen of cows fed grass and concentrates grew on a medium containing casein as the main substrate. Proteolytic counts for a cow fed on straw and concentrates or for a hay-fed cow were lower than counts for cows fed grass and concentrates, both in absolute terms and in relation to the total anaerobic count. In crude enzyme preparations derived from the rumen protozoa, amino acid arylamidase (leucine aminopeptidase)-like activity was the main proteolytic activity observed. In enzyme preparations extracted from the rumen bacteria in the presence of Triton X-100, trypsin-like activity was predominant. Amino acid arylamidase- and metal-chelating proteinase-like activity together with lower activities of carboxypeptidase A and B and a very low chymotrypsin-like activity were found as well. Studies with enzyme inhibitors showed that the bacterial trypsin-like activity was largely of the cysteine-protease type in a hay-fed cow, but in addition comprised serine-protease activity in a cow fed grass and concentrates. Total proteolytic activity of the enzymes in the bacterial fraction and the spectrum of proteolytic enzymes were found to vary with the ration.
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PMID:Characterization of microbial proteolytic enzymes in the rumen. 637 Jan 33

The degradation of normal human skin by the human polymorphonuclear leukocyte proteinases cathepsin G and elastase, and by a human skin chymotrypsin-like proteinase that appears to be a mast cell constituent, was examined. Enzymes were incubated with fresh, split-thickness skin for up to 8 h; the tissue was examined ultrastructurally and immunohistochemically using antibodies to known basement membrane constituents. In all cases, the primary damage observed was at the epidermal-dermal junction. Elastase degraded the lamina densa leaving scattered and disorganized anchoring fibrils, dermal microfibril bundles, and normal-appearing collagen fibers. Immunohistochemically, type IV collagen, laminin, KF1 antigen, and EBA antigen were absent. The bullous pemphigoid antigen was present and localized on the basal cells. Epidermal-dermal separation produced by the chymotrypsin-like proteinases, cathepsin G, and the human skin proteinase, was confined to the lamina lucida. The lamina densa and sub-lamina densa fibrillar network remained intact. The human skin chymotrypsin-like proteinase produced extensive epidermal-dermal separation, while cathepsin G, at comparable concentrations, produced only focal separations. Immunohistochemically, all antigens were present after incubation with enzyme. The bullous pemphigoid antigen, however, was found on the epidermal side of the split, while laminin was found on the dermal side. These results show that the epidermal-dermal junction is highly susceptible to neutral serine proteinases located in mast cells and polymorphonuclear leukocytes. Although all the proteinases produce epidermal-dermal separation, the patterns and extent of degradation are different. The distinctive patterns of degradation may provide a clue to the involvement of these proteinases in skin diseases.
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PMID:Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes. 638 17

The interaction of serine protease (esterases) with 6-chloro-2-pyrones was investigated. Time-dependent inactivation of chymotrypsin, alpha-lytic protease, pig liver elastase, and cholinesterase was found with 3- and 5-benzyl-6-chloro-2-pyrone, as well as 3- and 5-methyl-6-chloro-2-pyrone. No inactivation was observed with the unsubstituted 6-chloro-2-pyrone. The substituted pyrones did not inactivate papain or carboxypeptidase A, as well as a number of other nonproteolytic enzymes. The substituted chloropyrones, therefore, show considerable selectivity toward serine proteases. Analogues in which the 6-chloro substituent is replaced by H or OH do not inactivate. The presence of the halogen is, therefore, essential for inactivation. Chymotrypsin catalyzes the hydrolysis of 3-benzyl-6-chloro-2-pyrone. At pH 7.5, (E)-4-benzyl-2-pentenedioic acid is the major product, and 2-benzyl-2-pentenedioic anhydride is a minor product. The ration of hydrolysis product found to the number of enzyme molecules inactivated varies from 14 to 40. The enzyme inactivated with the 3-benzyl compound does not show a spectrum characteristic of the pyrone ring. This suggests that inactivation by 3-benzyl-6-chloro-2-pyrone occurs in a mechanism-based fashion after enzymatic lactone hydrolysis. When the enzyme is inactivated with the 5-benzyl compound, absorbance due to the pyrone ring is observed. We suggest that inactivation occurs through an active site directed mechanism involving a 1,6-conjugate addition of an active site nucleophile to the pyrone ring.
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PMID:Novel inactivators of serine proteases based on 6-chloro-2-pyrone. 641 Nov 20

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 formation of most connective tissue polysaccharides is initiated by transfer of D-xylose from UDP-D-xylose to specific serine residues in the core proteins of the putative proteoglycans. The substrate specificity of the xylosyltransferase catalyzing this reaction has not yet been examined in detail, but it appears that a -Ser-Gly- pair is an essential part of the substrate structure. Since the preparation of the known acceptors (e.g., Smith-degraded or HF-treated cartilage proteoglycan) involves a substantial effort, we have searched for readily available proteins with the -Ser-Gly-sequence, which might serve as alternative substrates. In the present work, it was found that silk fibroin from Bombyx mori, which consists, in large part, of the repeating hexapeptide, Ser-Gly-Ala-Gly-Ala-Gly, is an excellent substrate for the xylosyltransferase from embryonic chick cartilage. Pieces of silk were used directly in the reaction mixtures, and [14C]xylose transferred from UDP-D-[14C]xylose was measured by liquid scintillation spectrometry after rinsing the silk in 1 M NaCl and water. Substantially greater incorporation was observed with preparations of silk or fibroin which had been dissolved in 60% LiSCN and subsequently dialyzed exhaustively or diluted appropriately. Under standard reaction conditions, the Vmax for fibroin was 531 pmol/h/mg enzyme protein, as compared to 223 pmol/h/mg for Smith-degraded proteoglycan. Km values were 182 mg/liter (fibroin) and 143 mg/liter (Smith-degraded proteoglycan). The product of [14C]xylose transfer to silk was alkali labile, and [14C]xylitol was formed when [14C]xylosylsilk was treated with borohydride in alkali. Proteolytic digestion with papain, Pronase, leucine aminopeptidase, and carboxypeptidase A yielded a radioactive product which was identified as [14C]xylosylserine by electrophoresis and chromatography. The identity of the isolated [14C]xylosylserine was further supported by its resistance to treatment with alkali (0.5 M KOH; 100 degrees C; 8 h) and by acid hydrolysis which yielded [14C]xylose. Tryptic and chymotryptic fragments from fibroin were also good xylose acceptors and had Vmax values 60-70% of that observed for the intact protein. Substantial acceptor activity was displayed also by the sericin fraction of silk and by the silk sequence hexapeptide. Ser-Gly-Ala-Gly-Ala-Gly; the latter had a Vmax value close to 20% of that of intact fibroin.
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PMID:Silk--a new substrate for UDP-d-xylose:proteoglycan core protein beta-D-xylosyltransferase. 673 31

The effects of intracellular serine proteinase from B. amyloliquefaciens and of extracellular subtilisin BPN' on native and denaturated protein substrates were compared. The substrate hydrolysis by the enzymes was determined by a method initiating possible participation of intracellular serine protinease in intracellular protein degradation. This approach consists in a prolonged treatment of the products obtained after proteolysis with carboxypeptidase A with a subsequent amino acid assay. It was found that intracellular serine proteinase is capable of degrading denaturated protein substrates e. g. reduced, carboxymethylated ribonuclease A and bovine serum albumin, with an efficiency comparable to that achieved by subtilisin hydrolysis. On the other hand, the intracellular enzyme attacks the native proteins much slower than substilisin.
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PMID:[Specific features of intracellular serine proteinase of Bacillus amyloliquefaciens on native and denatured protein substrates]. 675 53


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