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)

Incubation of 2.5 microM benzo(a)pyrene (BaP) with C3H/10T 1/2 or CVP3SC6 (CVP) mouse fibroblasts for 48 hr resulted in the metabolism of 36 to 42% of the BaP to organic soluble derivatives, which cochromatographed with 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene, 9,10-trans-dihydroxy-9,10-dihydrobenzo(a)pyrene, 3-hydroxybenzo(a)pyrene, and 9-hydroxybenzo(a)pyrene, or to water-soluble derivatives. The formation of both organic and water-soluble metabolites during the 48-hr period increased proportionally with time, except in the case of BaP phenols, which increased initially but then remained the same or decreased. The distribution of organic soluble metabolites in the extracellular culture medium consisted primarily of BaP diols and was significantly different from that found inside the cells. The intracellular profile of organic soluble metabolites produced by both cell lines consisted predominantly of BaP phenolic derivatives and was qualitatively similar to the spectrum of metabolites produced by the incubation of BaP with C3H/10T 1/2 or CVP cell microsomes. The nature of the BaP water-soluble derivatives produced by the C3H/10T 1/2 and CVP cell lines was investigated by hydrolysis of culture medium with beta-glucuronidase and arylsulfatase. Although sulfation was not a major conjugation pathway for BaP in these cells, glucuronidation of BaP phenols was found to account for 30% of the total water-soluble derivatives. The similarity in the kinetics and qualitative nature of the metabolism of BaP by C3H/10T 1/2 and CVP cells indicates that both cell lines are equally capable of biosynthesizing the proximal carcinogen, 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene. Analysis of the water-soluble metabolites produced by these cells suggests further that the nonresponsiveness of the CVP cells to BaP-induced transformation cannot be accounted for on the basis of an increased detoxication of 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene.
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PMID:Metabolic activation of benzo(a)pyrene by transformable and nontransformable C3H mouse fibroblasts in culture. 628 46

The cellular localization of indoleamine 2,3-dioxygenase was studied in the mouse lung after induction by lipopolysaccharide treatment. No significant indoleamine 2,3-dioxygenase activity was detected in alveolar macrophages and type II epithelial cells, which were recovered by alveolar lavages and trypsin-treatment, respectively. To determine this enzyme activity in other types of lung cells, we prepared monodispersed lung cells (6.5 X 10(7) cells/lung) by incubation with 0.1% collagenase and 0.1% trypsin. In a Percoll isopycnic gradient, the dispersed cells were distributed with two peaks at the densities of 1.040 and 1.080 g/ml. The enzyme activity was recovered exclusively in the lighter fractions. As examined by electron microscopy or more quantitatively by using various marker enzyme activities, endothelial cells (angiotensin-converting enzyme as a marker enzyme of these cells), alveolar interstitial cells (prostaglandin dehydrogenase), type I epithelial cells, type II epithelial cells, alveolar macrophages (beta-glucuronidase), Clara cells (coumarin hydroxylase), and polymorphonuclear leucocytes (arylsulfatase) were distributed with peaks at the densities of 1.033, 1.040, 1.042, 1.045, 1.070, 1.082, and 1.093 g/ml, respectively. The distribution pattern of the indoleamine 2,3-dioxygenase activity exactly coincided with that of alveolar interstitial cells. The localization of this enzyme in alveolar interstitial cells was immunohistochemically confirmed with the anti-indoleamine 2,3-dioxygenase antibody.
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PMID:Induction of indoleamine 2,3-dioxygenase in alveolar interstitial cells of mouse lung by bacterial lipopolysaccharide. 634 79

Leupeptin, a nontoxic thiol protease inhibitor, has been proposed to have therapeutic use in hereditary muscular dystrophies. The purpose of this study was to characterize the in vivo changes in proteolytic activity of skeletal muscles induced by the repeated administration of leupeptin. Further, whether the modulation of proteolytic capacity by leupeptin affects the repair process of muscle injuries caused by heavy exercise was studied. Leupeptin was administered in mice intraperitoneally at a dose level of 15.5 mg/kg twice a day for 9 days. Leupeptin, known to be an inhibitor of cathepsin B both in vitro and after a single injection in vivo, paradoxically induced an increase of cathepsin B activity in mouse skeletal muscles after repeated administration. In addition, leupeptin administration for 9 days increased the activities of cathepsins C and D, as well as the rate of acid autolysis. The activity of beta-glucuronidase also increased, while those of arylsulfatase, ribonuclease, and alkaline protease were unaffected. No histopathologic changes were observed. At the low dosage used, leupeptin had no effect on the repair process of skeletal muscle after exercise injuries, although several proteolytic processes occur during the regeneration. It is suggested that the increase of acid protease activities in skeletal muscles is an adaptive response to the administration of the proteolytic inhibitor leupeptin and that leupeptin can be administered without prevention or delay of regenerative processes after the onset of myopathic changes.
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PMID:Effects of the protease inhibitor leupeptin on proteolytic activities and regeneration of mouse skeletal muscles after exercise injuries. 638 26

The structure of the major urinary metabolite of 4,4'-methylenebis(2-chloroaniline) (MBOCA) in dogs was identified and the reactivity of the metabolite was characterized in vitro. Arylsulfatase but not beta-glucuronidase hydrolyzed the metabolite in a time- and enzyme concentration-dependent manner. Electron impact mass spectrometry following derivatization and transesterification indicated that the major metabolite was ring hydroxylated and fast atom bombardment mass spectrometry confirmed the molecular weight as a sulfate ester. Proton nuclear magnetic resonance studies indicated that the ring substitution was ortho to an amine. These analytical and enzymatic data supported the proposed structure of the major urinary metabolite of MBOCA in dogs as 5-hydroxy-3,3'-dichloro-4,4'diaminodiphenylmethane-5-sulfate. Protein and DNA binding in vitro and mutagenicity were investigated. During hydrolysis with arylsulfatase, time- and enzyme concentration-dependent protein binding and time-dependent DNA binding were observed. Mutagenicity during enzymatic hydrolysis in the presence of Salmonella typhimurium TA1538 with up to 20 micrograms metabolite/plate was negative and at 50 micrograms/plate the metabolite was cytotoxic. These results indicated that the metabolite was the sulfate conjugate of a reactive molecule. This study demonstrated that the major metabolite of MBOCA in canine urine is an orthohydroxysulfate and thus is similar to the major metabolites of benzidine, 2-naphthylamine, and 4-aminobiphenyl.
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PMID:Structure elucidation and in vitro reactivity of the major metabolite of 4,4'-methylenebis(2-chloroaniline) (MBOCA) in canine urine. 654 68

In rat carrageenin pleurisy, both steroidal and non-steroidal anti-inflammatory drugs (SAID and NSAID respectively) produced a dose-related reduction of exudate volume and of prostaglandin (PG)E2 contents in the exudate at 3 h after carrageenin. However, with the exception of ketoprofen, administration of all the NSAID in low doses resulted in a significant reduction of PGE2 contents with no significant reduction in exudate volume. NSAID reduced leucocyte number and total activities of lysosomal enzymes in the exudate at 3 h after carrageenin only at the higher doses, while SAID did so in a dose-related manner. Both SAID and NSAID reduced the arylsulfatase activity released into the exudate (free activity) dose-relatedly but not the free activity of beta-glucuronidase at 3 h after carrageenin. However, some drug treatments resulted in a lower reduction in free arylsulfatase activity than in exudate volume. These results suggest that the reduction of PGE2 contents may be the main contribution to the anti-exudative activities of anti-inflammatory drugs in rat carrageenin pleurisy and that this effect may be complemented by the reduction of free activity of lysosomal enzymes such as arylsulfatase.
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PMID:Effects of several anti-inflammatory drugs on the various parameters involved in the inflammatory response in rat carrageenin-induced pleurisy. 658 58

Estrogen metabolism was studied in a newly established cell line (RL95-2) derived from a human endometrial carcinoma. Estradiol and estrone were metabolized to water-soluble derivatives by cells under in vitro culture conditions. Between 80-90% of the added steroids were metabolized, with nearly quantitative recovery of the products from the incubation medium. Arylsulfatase treatment converted the metabolites to ether-soluble forms, whereas beta-glucuronidase had no effect on the aqueous solubility of these compounds. Butanol extracts of the water-soluble estradiol metabolites cochromatographed on high performance liquid chromatography with 17 beta-estradiol-3-sulfate (93.6%) or estrone-3-sulfate (3.5%). No more than 6% of the estradiol added to the incubation medium was recovered in the form of estrone, either as estrone or estrone sulfate. After arylsulfatase treatment of the estradiol conjugates, 92% of the ether-soluble radioactivity cochromatographed with estradiol, and 3.8% cochromatographed with estrone. Estrogen-sulfurylating activity was localized in the cytosol of subcellular fractions of RL95-2 cells. The sulfoconjugation of estrogens by RL95-2 cells may prove useful as a model for the investigation of estrogen metabolism in endometrial carcinoma cells.
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PMID:Estrogen sulfoconjugation by human endometrial cancer cells (RL95-2) in culture. 669 41

Cunninghamella elegans metabolized 1- and 2-methylnaphthalene primarily at the methyl group to form 1- and 2-hydroxymethylnaphthalene, respectively. Other compounds isolated and identified were 1- and 2-naphthoic acids, 5-hydroxy-1-naphthoic acid, 5-hydroxy-2-naphthoic acid, 6-hydroxy-2-naphthoic acid, and phenolic derivatives of 1- and 2-methylnaphthalene. The metabolites were isolated by thin-layer and reverse-phase high-pressure liquid chromatography and characterized by the application of UV-visible absorption, 1H nuclear magnetic resonance, and mass spectral techniques. Experiments with [8-14C]2-methylnaphthalene indicated that over a 72-h period, 9.8% of 2-methylnaphthalene was oxidized to metabolic products. The ratio of organic-soluble in water-soluble metabolites at 2 h was 92:8, and at 72 h it was 41:59. Enzymatic treatment of the 48-h aqueous phase with either beta-glucuronidase or arylsulfatase released 60% of the metabolites of 2-methylnaphthalene that were extractable with ethyl acetate. In both cases, the major conjugates released were 5-hydroxy-2-naphthoic acid and 6-hydroxy-2-naphthoic acid. The ratio of the water-soluble glucuronide conjugates to sulfate conjugates was 1:1. Incubation of C. elegans with 2-methylnaphthalene under an 18O2 atmosphere and subsequent mass spectral analysis of 2-hydroxymethylnaphthalene indicated that hydroxylation of the methyl group is catalyzed by a monooxygenase.
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PMID:Transformation of 1- and 2-methylnaphthalene by Cunninghamella elegans. 669 8

Ovulated opossum oocytes are surrounded by a zona pellucida, but not by cumulus cells. Opossum sperm carry at least four acrosomal hydrolases (hyaluronidase, acrosin, N-acetylhexosaminidase, and arylsulfatase); the functions of these enzymes in opossum fertilization are uncertain. To identify possible substrates for these hydrolases, the ultrastructure of opossum oocytes was examined after fixation in the presence of ruthenium red which stabilizes extracellular matrices. This oocyte is unusual in having a wide perivitelline space containing a highly structured extracellular matrix (ECM). The ECM is comprised of granules and filaments, and it resembles matrices known to contain hyaluronic acid in other systems. Hydrolases, known to be present in opossum acrosomes, were tested for their effect on the ultrastructure of the zona pellucida and matrix of the perivitelline space. Trypsin dissolved the zona pellucida and decreased the size of the granules in the perivitelline space. Streptomyces hyaluronidase, which specifically attacks hyaluronic acid, removed only matrix filaments. Arylsulfatase, N-acetylhexosaminidase, and beta-glucuronidase did not affect the zona pellucida or ECM in our assay. These observations are consistent with the ideas that (1) opossum sperm must penetrate two oocyte investments, the zona pellucida and ECM of the perivitelline space; (2) the ECM contains hyaluronic acid (filaments) and protein (granules); (3) opossum sperm acrosin may function in penetration of the zona pellucida and ECM; and (4) opossum sperm hyaluronidase may function in penetration of the ECM by degrading hyaluronic acid (filaments). Dissolution of the granules and filaments from oocyte microvilli is probably necessary to permit close apposition and fusion of the sperm and oocyte membranes. The evolutionary significance of these results is discussed.
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PMID:Ultrastructure of opossum oocyte investing coats and their sensitivity to trypsin and hyaluronidase. 671 16

We have isolated from monkey (Macaca radiata) brain lysosomal fraction by phosphomannan-Sepharose chromatography a protein that binds four different lysosomal enzymes, beta-hexosaminidase, beta-glucuronidase, alpha-L-fucosidase and arylsulfatase. The isolated protein which appeared in an aggregated homogeneous form on gel electrophoresis under non-denaturing conditions at both pH 8.3 and pH 5.0 was found to be heterogeneous on SDS-gel electrophoresis with molecular weights less than 67,000. Binding was partly abolished by periodate treatment or by alkaline phosphatase treatment of the lysosomal enzymes. Binding was completely abolished by pronase digestion of the binding protein. Of the different sugars tested for inhibition of binding, mannose-6-phosphate was most effective followed by mannose and N-acetyl glucosamine while glucose and fucose were ineffective.
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PMID:A binding protein for lysosomal enzymes isolated from brain by phosphomannan-sepharose chromatography. 684 56

In bile specimens from postoperative patients with biliary drainage following cholecystectomy, in addition to unchanged dibromosulfophthalein (DBSP), a single polar metabolite of DBSP was found after i.v. injection of 5 mg/kg of the diagnostic dye. This metabolite, which has not previously been detected, was resistant to beta-glucuronidase and arylsulfatase and was remarkably stable in strongly acid and alkaline solutions. It exhibited the same spectrum and colour change interval as unchanged DBSP. Further studies of its identity revealed that it gave a ninhydrin-positive reaction and that its Rf-value on TLC could be restored by Raney-nickel reduction. Amino-acid analysis after reduction and acid hydrolysis showed an increase in glutamic acid and alanine that can be considered as splitting products of conjugated glutathione following these procedures. Estimation of the quantity of this possible glutathione conjugate indicates that it is formed less rapidly than the glutathione derivative of the tetrabromoanalogue BSP, and that it represents up to 25% of the total dye excreted in bile. The observed metabolism of DBSP in man may complicate its use in the study of hepatic transport function, and negates the previous assumption that, as in certain other animal species, the dye is excreted unchanged.
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PMID:Formation of a metabolite of dibromosulfophthalein (DBSP) in man. 687 53


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