Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three protein kinase C (PKC) activators (PMA, mezerein, and a diacylglycerol) had bidirectional effects on human polymorphonuclear neutrophil (PMN) degranulation responses to leukotriene (LT) B4. Lower concentrations of the three agents enhanced, whereas higher concentrations inhibited, release of lysozyme and beta-glucuronidase stimulated by the arachidonic acid metabolite. Contrastingly, the activators inhibited but never enhanced LTB4-induced Ca2+ transients. We examined the causes for these varying effects. Each PKC activator reduced PMN specific binding of [3H]LTB4. Scatchard analyses revealed that PMA (greater than or equal to 0.16 nM) decreased the number of high affinity LTB4 receptors. The receptor losses correlated closely with inhibition of Ca2+ transients. PMN pretreated with 0.5 nM PMA for 5 min retained approximately 50% of their high affinity LTB4 receptors. These cells responded to 10 nM LTB4 with reduced but still substantial rises in cytosolic Ca2+, enhanced PKC mobilization, and increased granule enzyme release. The latter two effects appeared calcium-dependent because sequential exposure to PMA and LTB4 did not synergistically stimulate PKC mobilization or degranulation in PMN that were: 1) Ca2(+)-depleted; 2) challenged with 5 nM PMA; or 3) treated with LTB4 for 5 min before PMA. Each of the latter treatments completely interfered with the extent or timing of LTB4-induced Ca2+ transients. Accordingly, we suggest that the response-specific, bidirectional effects of PKC activators on LTB4 result from two opposing mechanisms. First, PKC activators down-regulate LTB4 high affinity receptors and thereby reduce those PMN responses that are not elicited by activated PKC (i.e., Ca2+ transients). Second, LTB4, by elevating cytosolic Ca2+, increases the amount of PKC mobilized by PKC activators and thereby promotes PKC-dependent responses (e.g., degranulation). The two mechanisms may be pertinent to the bidirectional effects of PKC activators on various other agonists. Furthermore, PKC, by down-regulating receptors, may serve as a physiologic stop signal for terminating function and producing a poststimulatory state of desensitization.
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PMID:Mechanisms involved in the bidirectional effects of protein kinase C activators on neutrophil responses to leukotriene B4. 215 69

Trapping by magnetic polyethyleneimine (PEI) microcapsules was utilized to investigate the influence in male rats of dose, human dietary composition and time-dependence on reactive metabolites of benzo[a]pyrene (B[a]P) in the gastrointestinal (GI) tract; also, PEI microcapsules modified with copper phthalocyanine tetrasulphonic acid (CPTS) were tested in vivo for trapping of endogenous mutagens having planar molecular structure. In a preliminary experiment the PEI microcapsules were administered by gavage at 0, 24 and 48 h, with [14C]B[a]P at 2 h to chow-fed BDVI rats; microcapsules were recovered from faeces collected at 24, 48 and 72 h, and then subjected to an extraction sequence showing that the trapped B[a]P metabolites were inconsistent with B[a]P diol epoxide trapping (as previously found) and unaltered by elapsed time or 5-fold dose alteration of B[a]P. Then five groups of F344 rats were fed isocalorically either one of four low-fat human diets or rat chow; in order to investigate influences of diet both on B[a]P and endogenous mutagens, half of each group was tested at 2 weeks with this PEI microcapsule/[14C]B[a]P protocol and then at 3 weeks, PEI-CPTS microcapsules (two gavages). So as to provide a cross-over comparison, the other half of each group was first tested with PEI-CPTS microcapsules followed by PEI microcapsules/[14C]B[a]P 1 week later. The human diets were prepared from cooked British foods so as to simulate the adequate intake of all nutrients required by humans; but with 3-fold differences in intake levels of beef and dietary fibre non-starch polysaccharide (NSP), while ensuring the same intake of available energy, protein, fat and calcium. They gave very similar body-weight gains in the four groups but greatly reduced faecal weight, protein and total faecal enzyme activity compared with chow; the extraction pattern of microcapsule-trapped B[a]P metabolite radioactivity was not significantly altered. However, human diet consumption caused a 2- to 6-fold increase in B[a]P metabolite binding to microcapsules and reductions in microcapsule recovery, net 70-h B[a]P excretion, faecal protein and total activities for beta-glucuronidase and beta-galactosidase; these effects were more pronounced after 3 weeks, presumably due to prolonged dietary adaptation. Increased NSP in human diets significantly increased the B[a]P metabolite excretion and marginally reduced the microcapsule binding. The increase in microcapsule binding of B[a]P metabolites, interpreted as reflecting an increased amount of reactive metabolites encountered, was related to the dietary intake weight ratio of beef/NSP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulating effects in human diets of dietary fibre and beef, and of time and dose on the reactive microcapsule trapping of benzo[a]pyrene metabolites in the rat gastrointestinal tract. 215 56

The action of PGE1, PGE2, PGI2 and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca2+ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, beta-glucuronidase release (IC50 3-5 mumol/l) and Ca2+ influx while PGI2 and iloprost were ineffective at concentrations up to 10 mumol/l. These inhibitory actions of PGE1 and PGE2 were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI2 and iloprost. None of the prostaglandins affected the initial intracellular Ca2+ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE1 and PGE2 but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187). These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE1 and PGE2 might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i.e. inflammatory reactions.
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PMID:Cytotoxic enzyme release and oxygen centered radical formation in human neutrophils are selectively inhibited by E-type prostaglandins but not by PGI2. 215 12

Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses.
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PMID:Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. 216 79

We studied the effects of exogenous, purified phospholipase C (PLC) on neutrophil oxidative metabolism, lysosomal enzyme release and aggregation. We found that PLC inhibited O2- and H2O2 generation and oxygen consumption, but did not alter glucose oxidation via the hexose monophosphate shunt. In contrast, we found a striking stimulation of aggregation and release of the lysosomal enzymes lysozyme and beta-glucuronidase. In experiments designed to further characterize the mechanism of the PLC effect on membrane activation we studied the effect of PLC on intracellular calcium concentration [Ca2+]i and found that PLC did not interfere with the fMLP-mediated rise in [Ca2+]i, suggesting that its inhibitory effect on the respiratory burst does not involve inhibition of early signal transduction events. In addition, we found that PLC alone results in mobilization of intracellular Ca2+ stores, consistent with its stimulatory effect on aggregation and lysosomal enzyme release.
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PMID:Inhibition of polymorphonuclear leukocyte oxidative metabolism by exogenous phospholipase C. 216 37

Eosinophil granule major basic protein (MBP) and neutrophils have each been implicated in the inflammatory late phase events of allergic disease. Based on this association and flow cytometric evidence presented in this report for MBP binding to neutrophils, we examined the ability of MBP to activate human neutrophils. Incubation of neutrophils with 0.5 to 3.0 microM MBP at room temperature produced a concentration-dependent chemiluminescence (CL) response that peaked after 50 to 70 min. Reduced-and-alkylated MBP, eosinophil cationic protein, and eosinophil-derived neurotoxin did not induce CL. MBP-induced CL was abrogated in the absence of Ca2+ and was absent in neutrophils isolated from two individuals with chronic granulomatous disease. MBP also stimulated release of superoxide anion (O2-) and lysozyme but not beta-glucuronidase or lactate dehydrogenase. Additionally, 1.5 microM MBP in combination with FMLP or platelet-activating factor stimulated a synergistic increase in O2- release from cytochalasin B-treated neutrophils. The degree of synergism with FMLP or platelet-activating factor was inversely related (p less than 0.005) to the level of MBP-induced O2- release. These results indicate that MBP activates neutrophils in a noncytolytic fashion and provide evidence that eosinophil-neutrophil collaboration may contribute to the pathogenesis observed in allergic late phase reactions.
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PMID:Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release. 217 May 21

There were 41 postoperative patients of cholelithiasis with manifestation of Qi-Yin deficiency, had treated with Yiqi Yangyin Prescription. The regimens was 2 weeks as a course, thereafter bile specimens were taken through T tube drainage, and biochemical analysis were performed in order to determine the composition in consequence of the comparison of the treated patients with the control groups. There were 19 patients of bile pigment stone in whom 10 treated with the prescription and 9 were served as control. The results showed that the total bilirubin, unconjugated bilirubin, the concentration of calcium ion and the activity of beta-glucuronidase were markedly decreased as compared to those in the control group (P less than 0.05), the concentration of bile acid markedly increased than that in the control group (P less than 0.05). There were 22 patients of cholesterol stone, 11 treated with the prescription and 11 were served as control group. The results were the same as in bile pigment stone group except decreased in conjugated bilirubin (P less than 0.05), and the unconjugated bilirubin were remained unchanged (P greater than 0.05) as compared to the control group. The ratio of unconjugated bilirubin to total bilirubin and the ratio of bile acid to bilirubin were markedly decreased as compared to those in the control group. The above observation showed promptly that Yiqi-Yangyin Prescription gave a promise influence on lithogenic bile of cholelithiasitic patients, and also investigated the mechanism of the prescription used for deficiency patients with biliary troubles.
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PMID:[Effect of yiqi-yangyin prescription on bile composition of cholelithiasis patients]. 220 33

In the present communication we report that fibroblasts, isolated from human gingiva obtained from 13 different patients, secreted soluble product(s) which can promote bone resorption in vitro. Fibroblasts were isolated from explants of human gingiva, subcultured, grown to confluent monolayers, subsequently cultured in growth arrest media for 0-72 h and conditioned media harvested. Bone resorption was assessed in cultured mouse calvarial bone by quantifying the mobilization of minerals and the release of lysosomal enzymes. Human fibroblast-conditioned media (HFCM) dose-dependently stimulated the release of 45Ca from prelabelled bones and the mobilization of stable calcium and inorganic phosphate from unlabelled bones. In addition, HFCM increased the release of beta-glucuronidase and beta-N-acetylglucosaminidase from the calvaria. No effect of HFCM on the release of 45Ca from dead bones could be seen. HFCM caused a dose-dependent increased degradation of bone matrix proteins, as assessed by the release of 3H from [3H]proline-labelled calvaria. The stimulation of 45Ca release could already be seen after 3-12 h of treatment. Treatment of the bones with HFCM for 12 h was sufficient to obtain a prolonged stimulation of 45Ca release. Bones cultured in the presence of HFCM showed an increased number of osteoclasts. Calcitonin, but not indomethacin, inhibited 45Ca release stimulated by HFCM. Ultrafiltration of HFCM did not cause any loss of the 45Ca release response. The amount of bone-resorbing activity produced by the gingival cells was proportional to the number of cells. In addition, HFCM stimulated the proliferation of human fibroblasts and osteoblast-enriched mouse calvarial bone cells. It is concluded that human gingival fibroblasts secrete one or several factors that can stimulate osteoclastic bone resorption in vitro by a prostaglandin-independent pathway.
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PMID:Stimulation of bone resorption and cell proliferation in vitro by human gingival fibroblasts from patients with periodontal disease. 222 7

Bile was obtained from 82 patients with various biliary tract diseases and concentrations of prostagloandins, leukotriens, mucin, and a number of lithogenic components were measured in order to evaluate the role of these substances in the pathogenesis of gallstone formation. The characteristics of bile in cases of cholesterol gallstones included high concentrations of prostaglandins and hexosamine and a high cholesterol saturation index. Prostaglandin E2 and prostaglandin F2 alpha concentrations in bile were correlated with hexosamine concentration, and prostaglandins and hexosamine were found to be actively synthesized and secreted in the gallbladder. Prostaglandins E2 and F2 alpha may therefore stimulate mucin secretion in the gallbladder with supersaturated bile. The characteristics of bile in cases of calcium bilirubinate gallstones included a high detection rate for bacteria, high beta-glucuronidase activity, a high percentage of unconjugated bilirubin, a low cholesterol saturation index and high concentrations of prostaglandins and hexosamine. Moreover, the synthesis and secretion of prostaglandins in the biliary tract were accelerated in cases of infected bile. Thus, hypersecretion of mucin, stimulated by prostaglandins, my participate in the onset and development of biliary tract infection or in the formation of calcium bilirubinate gallstones. Regarding the role of prostaglandins and mucin, the hypotheses for gallstone formation previously reported by many authors are supported by the clinical data obtained in the current study.
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PMID:The pathophysiological characteristics of bile from patients with gallstones: the role of prostaglandins and mucin in gallstone formation. 230 78

The effects of dietary calcium, magnesium, and butterfat on intestinal function and flora in rats initiated with 1,2-dimethylhydrazine (DMH) were studied. Male weanling rats were assigned to six isocaloric diets that varied in their levels of calcium and magnesium (0.25% Ca with 0.05% Mg, 1.0% Ca with 0.05% Mg, or 0.625% Ca with 0.50% Mg) and butterfat (5% or 20%). One-half of the rats in each treatment were injected subcutaneously with DMH weekly for four weeks. This short-term exposure to DMH increased colonic ornithine decarboxylase (ODC) activity and the mass of cecal contents. Ingestion of the high levels of either calcium or magnesium depressed colonic ODC activity and depressed apparent absorption of organic matter, calcium, magnesium, and phosphorus. Ingestion of excess magnesium increased the mass of the cecal contents by twofold, caused hypertrophy of cecal walls, and increased the total amount of protein and total nitroreductase and beta-glucuronidase activity in the ceca of rats. Ingestion of supplemental calcium had less dramatic effects and increased the mass of cecal contents by only 28% and decreased the total amount of protein in the ceca. On the basis of their different effects on cecal microflora, magnesium appears to have less potential than does calcium as a protective agent against colon cancer.
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PMID:Changes in intestinal function of rats initiated with DMH and fed varying levels of butterfat, calcium, and magnesium. 230 74


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