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)

The potency of the calcium ionophore A23187 in inducing three activities of human leukocytes (histamine secretion from basophils, enzyme secretion from PMNs, and proliferation of lymphocytes) was markedly dependent on the solvent (DMSO versus ethanol versus aqueous buffer) used for its initial sonication. While 0.1 micrograms/ml of DMSO- and ethanol-solubilized A23187 induced maximal histamine release from basophils and histaminase release from PMNs, concentrations of aqueous buffer-sonicated ionophore of greater than or equal to 1 microgram/ml were required for an equivalent response. Ionophore sonicated in organic solvents caused a maximum release of 40% of PMN beta-glucuronidase, at an optimal concentration tenfold higher than that required for maximal histaminase release; ionophore sonicated in aqueous buffers, even at high concentrations, effected a release of less than 5% of cellular beta-glucuronidase. A23187 also induced lymphocyte proliferation over a narrow concentration range; 0.05 micrograms/l of DMSO-sonicated ionophore induced optimal proliferation and concentrations greater than or equal to 0.2 micrograms/ml were toxic. Twofold higher concentrations of ethanol-sonicated ionophore and fourfold higher concentrations of aqueous-sonicated ionophore were necessary for maximal proliferation, and the magnitude of the maximal response with aqueous-sonicated A23187 was only one-half that of DMSO-solubilized agent. Ionophore-induced release of histamine from basophils and enzymes from PMNs was not cytotoxic, since ionophore induced neither LDH nor histamine release from heat-treated (47 degrees C) cells. These results explain several previous, discordant reports on the presence or absence of an effect of A23187 on cellular secretory events, on differing dose-response relationships, and on cytotoxic versus noncytotoxic mechanisms of action.
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PMID:Effect of solvent on the histamine-releasing, enzyme-releasing, and mitogenic properties of the calcium ionophore A23187. 9 71

Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of beta-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development.
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PMID:Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation. 22 36

The effects of DMSO are thought to result from the formation of hydrogen bonds with proton-donor groups on biopolymers, which are stronger than those formed with water. Since DMSO contains methyl groups, however, effects on hydrophobic bonding in proteins could be expected at higher DMSO levels. Our studies of the effects of DMSO on model subunit proteins can be interpreted in the above terms. At a concentration of 20% or less, DMSO changed glutamate dehydrogenase into the inactive monomer and the effects were fully reversible with the activator (ADP). Higher DMSO levels resulted in irreversible inactivation. The predominant effect noted on beta-glucuronidase was irreversible inactivation by 20% or more DMSO at 37 degrees C. Purified beta-glucuronidase exhibited an activation in 20% DMSO at high substrate levels; this resulted from an apparent substrate inhibition in the absence of DMSO. DMSO inhibited the clotting of fibrinogen by purified thrombin, but the major effect appeared to be due to competition between thrombin and DMSO for binding sites on fibrinogen. These effects appear to be largely due to interactions between DMSO and hydrophobic bonding in fibrinogen, although DMSO also appears to interfere with the aggregation of fibrin monomers through its effects on hydrophilic groups. These results suggest that reversible alterations in protein structure are the major effect of exposure of subunit proteins to low DMSO levels at low temperatues, while irreversible denaturation of subunit proteins may be an appreciable effect a higher temperatures and higher DMSO concentrations.
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PMID:Effects of dimethyl sulfoxide on subunit proteins. 23 13

Cyclosporin (Cs)A but not CsH inhibits activation of human lymphocytes. We studied the effects of CsA, CsD, and CsH on human neutrophil activation induced by chemoattractants and by various substances that circumvent receptor stimulation. CsH inhibited superoxide (O2-) formation induced by the chemotactic peptide, FMLP (30 nM), with a half-maximal effect at 40 nM. O2- formation was abolished by CsH at 1 microM. CsH increased the concentration of FMLP causing half-maximal activation of O2- formation from 30 nM to 0.8 microM and substantially reduced the stimulatory effect of FMLP at supra-maximally effective concentrations. The inhibitory effect of CsH on O2- formation was evident immediately after addition to neutrophils. CsH also markedly inhibited the increase in cytosolic Ca2+ ([Ca2+]i), beta-glucuronidase, and lysozyme release and aggregation stimulated by FMLP. CsA and CsD were considerably less effective than CsH to inhibit FMLP-induced O2- formation. CsA and CsD were without effect on exocytosis, rises in [Ca2+]i, and aggregation induced by the chemotactic peptide. Cyclosporines inhibited FMLP-induced O2- formation in an additive manner, indicating that they acted through a mechanism they had in common. Cyclosporines only slightly inhibited O2- formation and lysozyme release induced by C5a. Aggregation and rises in [Ca2+]i stimulated by C5a were not affected by cyclosporines, and they did not inhibit O2- formation and exocytosis induced by platelet-activating factor and leukotriene B4. Cyclosporines partially inhibited O2- formations induced by NaF and gamma-hexachlorocyclohexane. CsA marginally inhibited PMA-induced O2- formation and lysozyme release. CsA, CsD, and CsH did not inhibit arachidonic acid-induced O2- formation and its potentiation by NaF or stable guanine nucleotides in a cell-free system from DMSO-differentiated HL-60 cells. CsH partially inhibited binding of FML [3H]P to formyl peptide receptors in membranes from DMSO- or dibutyryl cAMP-differentiated HL-60 cells. Our data show that: 1) cyclosporines differentially inhibit activation of human neutrophils; and 2) CsH is, indeed, not immunologically inactive but is a potent and effective inhibitor of FMLP-induced O2- formation. 3) CsH interferes with agonist binding to formyl peptide receptors and in addition, cyclosporines may also act at sites distal to chemoattractant receptors.
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PMID:Differential inhibition of human neutrophil activation by cyclosporins A, D, and H. Cyclosporin H is a potent and effective inhibitor of formyl peptide-induced superoxide formation. 165 6

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 urine of mice injected intraperitoneally with pyrene during exposure to NO2 was found to contain highly mutagenic compounds by means of the Ames test using Salmonella typhimurium strain TA98. The mice were exposed to 20 ppm NO2 for 3 days before intraperitoneal injection of pyrene (800 mg/kg of body weight). The pyrene-treated mice were further exposed to NO2 for an additional 24 hr, and the urine from the mice was collected in ice-cooled containers and stored frozen in the dark. The collected samples were treated with beta-glucuronidase and passed through activated Sep-Pack C18 cartridges. After elution with methanol, the effluent was concentrated and the residue was dissolved in dimethyl sulfoxide (DMSO). The DMSO solution was fractionated by high-performance liquid chromatography and the mutagenicity of each fraction was assayed with S. typhimurium strain TA98. The mutagenic compounds 3-hydroxy-1-nitropyrene, 6-hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 1-hydroxypyrene were identified in the mutagenic fractions by mass spectrometry and UV-visible spectrophotometry with synthetic reference substances. These mutagenic compounds may have been formed by either nitration of hydroxylated pyrene, or hydroxylation of 1-nitropyrene, which is formed in vivo from pyrene and NO2, or the simultaneous occurrence of these two reactions in the mouse body.
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PMID:Detection of mutagenic compounds in the urine of mice administered pyrene during exposure to NO2. 311 37

Lysosomal preparations were exposed to various concentrations of dimethylsulphoxide (DMSO) and aspirin singularly and in combination. Acid phosphatase and beta-glucuronidase activities were measured and utilized as an indication of lysosomal membrane stability under experimental conditions in the presence and absence of these drugs. Extremely low concentrations of each drug were employed in an attempt to mimic the levels which might be feasible in vivo. There was a significant decrease of enzyme activity (increased structure-linked latency) in the presence of DMSO. Aspirin had no significant effect on the latency of the lysosomes. There was no indication of synergism between DMSO and aspirin. It was concluded that some of the therapeutic advantages attributed to DMSO in the treatment of arthritis and other musculoskeletal diseases may come from the stabilization of lysosomes in cells that contribute to the pathological condition. Aspirin did not seem to exert a therapeutic effect through this mechanism.
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PMID:The effects of aspirin and dimethyl sulphoxide on the latency of lysosomes in a cell-free system. 672 49

Atrazine (ATZ), an s-triazine herbicide, is a widespread environmental contaminant. The hepatocarcinogenic component of technical grade dinitrotoluene, 2,6-dinitrotoluene (2,6-DNT, 19.5%), is a byproduct of trinitrotoluene synthesis and is found at production sites. This study explores the effect of ATZ treatment on the bioactivation of the promutagen, 2,6-DNT. Male Fischer 344 rats (5 weeks old) were administered 50 mg/kg of ATZ by gavage for 5 weeks. At 1, 3, and 5 weeks, both DMSO-control and ATZ-pretreated rats were treated p.o. with 75 mg/kg of 2,6-DNT and were housed in metabolism cages for urine collection. Sulfatase- and beta-glucuronidase-treated, concentrated urine was bioassayed for urinary mutagens in a microsuspension modification of the Salmonella assay with and without metabolic activation. No significant change in mutagen excretion was observed in ATZ-treated rats; however, an elevation in direct-acting urine mutagens from rats receiving ATZ and 2,6-DNT at weeks 1 (359 +/- 68 vs. 621 +/- 96 revertants/ml) and 5 (278 +/- 46 vs. 667 +/- 109 revertants/ml) of treatment was observed. The increase in production of urinary mutagens was accompanied by an elevation in small intestinal nitroreductase activity. Increases in large intestinal nitroreductase and beta-glucuronidase were observed after 5 weeks. There was no apparent effect of ATZ following 5 weeks of treatment on the production of 2,6-DNT-derived hepatic DNA adducts. ATZ treatment modifies intestinal enzymes responsible for promutagen bioactivation, and potentiates the excretion of mutagenic urine in 2,6-DNT-treated animals.
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PMID:Atrazine treatment potentiates excretion of mutagenic urine in 2,6-dinitrotoluene-treated Fischer 344 rats. 755 15

The nature of the compartmentalization of catalase in human myeloid cells is an unresolved issue. Using a rabbit polyclonal antibody specific for catalase, indirect immunocytofluorescence of immature leukemic promyelocytes (HL-60 cells) showed a pattern of small, sharp, punctate staining in the cytoplasm of all cells, while mature neutrophils showed a larger diffuse, flocculent pattern of cytoplasmic staining. Differential centrifugation of nitrogen cavitates of HL-60 cells indicated that the putative catalase-containing compartment was relatively fragile compared with the compartment(s) that contained myeloperoxidase (MPO), beta-hexosaminidase, beta-glucuronidase, and lysosomal alpha-mannosidase activities. Parallel studies using dimethylsulfoxide (DMSO)-induced HL-60 cells and mature neutrophils showed that, in the course of differentiation, there was an apparent shift in the localization of catalase from the granule fraction to the cytosolic fraction. Percoll-sucrose density gradient centrifugation of HL-60 cell cavitates showed a catalase-containing compartment with a mean peak density (1.05 g/mL) significantly lower than that of the major myeloperoxidase-containing compartment (1.08 g/mL); in mature neutrophils, catalase activity comigrated with lactate dehydrogenase (LDH) activity. Catalase in isolated fractions was protected from proteolysis in the absence, but not in the presence, of 0.1% Triton X-100. Digitonin titration experiments confirmed the compartmentalized nature of catalase in immature HL-60 cells and were consistent with a cytosolic localization in mature neutrophils. Ultrastructural localization of catalase by Protein A-gold immunocytochemistry demonstrated four to six catalase-containing compartments in all HL-60 cell profiles. In mature neutrophils, catalase was localized primarily in the cytoplasmic matrix, although in fewer than 2% of the cell profiles, one to two catalase-containing compartments were observed. The changes in catalase localization that occur during myeloid differentiation appear to be similar to the changes that occur during erythroid and megakaryocytic differentiation, and may have potential clinical significance in the classification of acute leukemia and in the development of drug resistance.
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PMID:Changes in the localization of catalase during differentiation of neutrophilic granulocytes. 816 45

The production and storage of explosives has resulted in the environmental accumulation of the mutagen 2,4,6-trinitrotoluene (TNT). In order to characterize the production of mutagenic urinary metabolites, 6-week old male Fischer 344 rats were administered 75 mg of TNT/kg or DMSO vehicle by gavage. The animals were placed into metabolism cages, and urine was collected for 24 hr. Following filtration, metabolites in the urine were deconjugated with sulfatase and beta-glucuronidase and concentrated by solid phase extraction. The eluate was fractionated by reverse-phase high-performance liquid chromatography (HPLC) using acetonitrile/water, and the fractions, were solvent exchanged in DMSO by nitrogen evaporation. Each HPLC fraction was bioassayed in strains TA98, TA98NR, TA100, and TA100NR without metabolic activation using a microsuspension modification of the Salmonella histidine reversion assay. Fractions 3, 5-18, 21, 22, and 24-26 contained mutagens detected by strain TA98. In the nitroreductase-deficient strain TA98NR, some mutagenic activity was lost; however, fractions 3, 6, 9-11, 15, and 25 clearly contained direct-acting mutagens. Fewer fractions were positive in strain TA100 (9-16, 19, 20, and 25) with less activity observed in the nitroreductase deficient strain TA100NR (fractions 3, 12, 14, 15, and 25). Although some mutagenic activity coeluted with known TNT metabolite standards, there were still many unidentified mutagenic peaks.
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PMID:Mutagenicity of HPLC-fractionated urinary metabolites from 2,4,6-trinitrotoluene-treated Fischer 344 rats. 936 8


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