Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of PGD2 and its mimetic ZK 110.841 ((5Z,13E)-(9R,11R,15S)-9-chloro-15-cyclohexyl-11,15- dihydroxy-16,17,18,19, 20-pentanor-5,13-prostadienoic acid) was compared to PGE1 in vitro on superoxide anion generation, degranulation, leukotriene (LT) B4 release and Ca++ fluxes in human polymorphonuclear leukocytes (PMN). All compounds were potent inhibitors of formyl-methionyl-leucyl-phenylalanine (FMLP)- and platelet-activating factor (PAF)-induced superoxide anion generation, beta-glucuronidase release and Ca++ influx. The PAF-induced release of LTB4 in the presence of 10 mumoles/l arachidonic acid was significantly attenuated by these prostaglandins. This inhibition of PMN function was paralleled by an increase in cellular cAMP levels. The molar potency of the prostaglandins used was comparable, although the D-type compounds appeared slightly more potent in some PMN function tests. None of the substances affected PMN activation induced by the calcium inophore calcimycin (A23187). The data demonstrate an effective inhibition of receptor-mediated (FMLP, PAF) PMN activation by PGD2 and its mimetic ZK 110.841, suggesting either an inhibitory PGD2 receptor on human PMN or action of PGD2 at the PGE receptor. PGD2 is a labile compound in vivo and is rapidly metabolized into a number of products with different biological properties. Since ZK 110.841 lacks this instability, this compound may serve as an important tool to classify PGD2-mediated reactions.
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PMID:PGD2 and its mimetic ZK 110.841 are potent inhibitors of receptor-mediated activation of human neutrophils. 164 6

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

The effect of dimethylsulfoxide (DMSO) on the level of prostaglandins (PGE and PGF2 alpha), the intensity of peroxide oxidation of lipids (POL), activity of beta-glucuronidase (BGU) prior to and 5 and 24 hours after application made to the patients' hands was studied by a double blind method in 20 patients with genuine rheumatoid arthritis (RA) against the background of therapy with nonsteroid antiphlogistic preparations. Of 20 patients 10 received one-hour application of a 50 per cent DMSO gel, 10 patients received placebo (glycerol instead of DMSO). The authors revealed a significant suppression of PS production against the background of an increased level of POL in four patients who had been given DMSO. The activity of BGU increased five hours after application of DMSO and in 24 hours returned to the initial levels. Changes in the levels of inflammation mediators proved to be statistically insignificant in the group of patients given placebo. Thus, one-hour application of DMSO produced a substantial effect on the system of mediators and their interrelationship in patients with RA.
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PMID:[Effect of 1-hour administration of dimethyl sulfoxide on the levels of prostaglandins, products of lipid peroxidation and beta-glucuronidase activity in the blood of patients with rheumatoid arthritis]. 260 62

The use of prostaglandins is currently undergoing clinical trials in respiratory failure accompanying sepsis. The effect of prostaglandin E1 (PGE1) and prostacyclin (PGI2) infusion on endotoxin-induced lung injury, with attention to interstitial fluid flux (QL), pulmonary vascular pressure (Ppa), leukocytes, platelets, and release of the lysosomal enzyme beta-glucuronidase, was investigated. A chronic lung lymph fistula model in sheep was used. Seven sheep alternately received Escherichia coli endotoxin and endotoxin plus PGE at a dosage of 1 microgram/kg/min. Six sheep received PGI2 (0.2 microgram/kg/min) instead of PGE1. Both PGE1 and PGI2 decreased the pulmonary hypertension and the interstitial edema produced by endotoxin primarily through their vasodilatory properties. Prostacyclin seemed to have an additional membrane-stabilizing effect. A rebound increase in QL, Ppa, and platelets occurred when PGE1 or PGI2 infusion was discontinued.
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PMID:Prostaglandin infusion and endotoxin-induced lung injury. 703 77

Pectin is a partially methoxylated polymer of galacturonic acid obtained from fruits. Among pectin, apple pectin exerts stronger bacteriostatical action on Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa and Escherichia coli in comparison with citrus pectin. In this study, we used water-soluble methoxylated pectin from apple. The diet, supplemented by 20% apple pectin, significantly decreased the number of tumors and the incidence of colon tumor. PGE2 level in distal colonic mucosa in 20% apple pectin fed rats were lower than those in basal diet fed rats. Fecal beta-glucuronidase activities in the apple pectin fed group, which has been considered a key enzyme for the final activation of Dimethylhydrazine metabolism to carcinogens in the colonic lumen, were signifieantly lower than those in control group at initiation stage of carcinogenesis. In the case the concentrations of beta-glueosidase and azoreductase were also decreased. The effect of apple pectin on the colon carcinogenesis may partially depend on PGE, concentration decrease in colonic mucosa and on the type of pectin, also related to fecal enzyme activities.
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PMID:Anticarcinogenic action of apple pectin on fecal enzyme activities and mucosal or portal prostaglandin E2 levels in experimental rat colon carcinogenesis. 914 58

Metabolic acidosis increases urine calcium excretion without an increase in intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro, metabolic acidosis has been shown to initially induce physicochemical mineral dissolution and then enhance cell-mediated bone resorption. Acidic medium stimulates osteoblastic prostaglandin E(2) production, which mediates the subsequent stimulation of osteoclastic bone resorption. Glucocorticoids are also known to decrease bone mineral density, and metabolic acidosis has been shown to increase glucocorticoid production. This study tested the hypothesis that glucocorticoids would exacerbate acid-induced net calcium efflux from bone. Neonatal mouse calvariae were cultured in acid (Acid; pH = 7.06 +/- 0.01; [HCO(3)(-)] = 10.6 +/- 0.3 mM) or neutral (Ntl; pH = 7.43 +/- 0.01; [HCO(3)(-)] = 26.2 +/- 0.5 mM) medium, with or without 1 microM cortisol (Cort), and net calcium efflux and medium prostaglandin E(2) (PGE(2)) levels and osteoclastic beta-glucuronidase activity were determined. Compared with Ntl, Cort alone decreased calcium efflux, medium PGE(2), and osteoclast activity; Acid led to an increase in all three parameters. The addition of Cort to Acid led to a reduction of calcium efflux, medium PGE(2) levels and beta-glucuronidase activity compared with Acid alone. There was a significant direct correlation between medium PGE(2) concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between osteoclastic beta-glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE(2) concentration and beta-glucuronidase activity (r = 0.976; n = 4; P < 0.01). Thus, in vitro cortisol inhibits acid-induced, cell-mediated osteoclastic bone resorption through a decrease in osteoblastic PGE(2) production. These results suggest that the osteopenia observed in response to metabolic acidosis in vivo is not due to an increase in endogenous cortisol production.
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PMID:Cortisol inhibits acid-induced bone resorption in vitro. 1223 42

Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose oil (PO) on the ability of stimulated leukocytes to produce inflammatory mediators was investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2% by weight of corn oil) or diets containing 15% by weight of VOO, PO, or FO. After 8 weeks, glycogen-elicited peritoneal polymorphonuclear leukocytes, mainly neutrophils, were isolated. The calcium-ionophore stimulated neutrophils (2.5 x 10(6) cells/mL) obtained from rats fed the different oils produced a higher release of lysosomal enzymes (beta-glucuronidase, lysozyme, and myeloperoxidase [MPO]) compared with those fed BD. The production of reactive oxygen species (ROS) in response to the stimulant, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), by neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol of H(2)O(2)) was similar to the BD group (12.01 nmol O(2)(-) and 8.49 nmol H(2)O(2)) and significantly lower than the PO (20.90 nmol O(2)(-) and 10.84 nmol H(2)O(2)) and FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups. The cyclooxygenase-derived eicosanoid production was reduced by the lipid enrichment of the diets. Whereas the generation of prostaglandin E(2) (PGE(2)) was significantly decreased in VOO (5.40 ng/mL), PO (4.95 ng/mL), and FO (1.44 ng/mL) groups compared with BD (8.19 ng/mL), thromboxane B(2) (TXB(2)) reduction was especially significant in neutrophils from the FO diet group (14.67 ng/mL compared with 26.69 ng/mL from BD). These experimental data suggest that FO and PO, as well as VOO, could be considered a valuable strategy in preventing the generation of some inflammatory mediators.
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PMID:Effects of different dietary oils on inflammatory mediator generation and fatty acid composition in rat neutrophils. 1468 43

Human PMN release lysosomal enzymes (beta-glucuronidase, acid phosphatase) when exposed to immune complexes, but do not release cytoplasmic LDH. The cells remain viable, and failure of LDH to appear in supernatants is not due to selective absorption or inactivation. Release of enzymes is not due to platelet contamination and is only partially enhanced by fresh serum. The selective release of lysosomal enzymes after uptake of complexes resembles that induced by inert particles of zymosan, and can be distinguished from the concurrent release of all enzymes after cell death induced by membrane-lytic crystals of MSU. Uptake of complexes, zymosan, or MSU particles is accompanied by concomitant increases in C-1 oxidation of glucose. Although MSU-induced damage can be retarded by the presence of Tris buffer, immune complexes and zymosan selectively release lysosomal hydrolases in the presence or absence of Tris buffer. Agents which elevate the level, within cells, of cAMP (PGE(1), theophylline, 2-CA) and cAMP itself inhibit the selective extrusion of acid hydrolases from leukocytes without affecting the viability of cells. Leukocytes may respond to immune particles by regurgitating a portion of their lysosomal hydrolases during phagocytosis.
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PMID:Mechanisms of lysosomal enzyme release from leukocytes exposed to immune complexes and other particles. 1986 63

We investigated the in vitro effects of the pneumotoxic agents, silica and asbestos, and the relatively innocuous materials, aluminium oxide (Al(2)O(3)) and titanium dioxide (TiO(2)), on alveolar macrophages (AM) using endpoints reflecting the cytotoxic and AM activating properties of the dusts. Rat AM were exposed in vitro (24 hr) to 10-1000 mug/ml of the dusts. AM conditioned media was analysed for lactate dehydrogenase (cytotoxicity), beta-glucuronidase (lysosomal enzyme), leukotriene B4 (LTB4), prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF) and interleukin-1 (IL-1). AM LTB4 and TNF release were increased by silica and asbestos but not by Al(2)O(3) or TiO(2). IL-1 release was not affected, and changes in PGE(2) release were minimal, after dust exposure. Cytotoxic activity was not consistently associated with LTB4, TNF or beta-glucuronidase release. The ability of silica and asbestos, but not Al(2)O(3) and TiO(2), to activate AM to release the pro-inflammatory mediators, LTB4 and TNF, may be responsible, at least in part, for the greater inflammation and pneumotoxicity associated with silica and asbestos exposure. These findings suggest that assessment of AM mediator secretion in vitro can provide information to understand better the potential of a material to cause respiratory toxicity.
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PMID:Differential effects of mineral dusts on the in vitro activation of alveolar macrophage eicosanoid and cytokine release. 2070 79