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)

Human monoblastoid cell line U-937 was adapted to grow in protein-free (protein-free hybridoma--PFH) medium and cloned by limiting dilution. Resulting cell subline (U-937/PF) cultured in protein-free medium was characterized by immunological, cytochemical and biochemical techniques. There were no major differences in immunophenotype (determined by FACS analysis with monoclonal antibodies directed to HLA and CD antigens) and cytochemical markers between the U-937/PF cells cultured in protein-free cell culture medium and parental U-937 cell cultured in serum-supplemented medium. Maximal cell density was slightly decreased in protein-free culture as compared to the parental cell line in FCS-supplemented medium. Cell viability and cell DNA histograms (determined by propidium iodide cytofluorimetry) showed no major differences between parental U-937 and U-937/PF cells. Phorbol ester (TPA)-induction of differentiation-associated cell markers resulted in a proliferation arrest and accumulation of G0/G1 cells in both sublines. All-trans retinoic acid and, to a lesser extent, TPA-stimulated NBT reduction was higher in parental U-937 cells cultured in serum-supplemented medium as compared to U-937/PF cells. Quantitative differences in the expression and inducibility of some cytochemical markers (beta-glucuronidase, chloroacetate esterase) were found between both examined sublines. Described U-937/PF subline cultured in a protein-free cell culture medium (PFH) appeared as a potential tool for studies of in vitro inducing agents and serum components with differentiation promoting (or inhibiting) activities.
 ...
PMID:Human monoblastoid cell line U-937 cultured in protein-free medium: immunophenotype, cytochemical and biochemical markers. 195 65

When rabbits and humans are treated with orally administered 13-cis retinoic acid, the retinoic acid and a more polar retinoid metabolite appear in tears and lacrimal gland fluid. This study tested the hypothesis that this metabolite was a retinoyl-beta-glucuronide. Lacrimal gland fluid from rabbits treated with a pharmacologic dose of 13-cis retinoic acid was analyzed. Based on chromatographic retention time, absorbance maximum, and degradation to 13-cis retinoic acid by the enzyme beta-glucuronidase, it was shown that this retinoid metabolite is 13-cis retinoyl-beta-glucuronide. The 13-cis retinoyl-beta-glucuronide was also extracted from the lacrimal gland itself. It is concluded that 13-cis retinoyl-beta-glucuronide is a major metabolite of 13-cis retinoic acid in the rabbit and that this retinoid is secreted by the lacrimal gland.
 ...
PMID:13-cis retinoyl-beta-glucuronide in lacrimal gland fluid of rabbits treated with 13-cis retinoic acid. 209 16

Eight metabolites of retinol were isolated by high-performance liquid chromatography (HPLC) from the plasma of the non-human primate Macaca fascicularis after acute exposure to 150,000 IU of vitamin A per kilogram body weight. After enrichment and further chromatographic purification, the metabolites were reinjected individually into a second HPLC system which was connected on-line by a thermospray interface to a mass spectrometer operated in the positive ionization mode. Six retinoids were identified by (i) a comparison of their retention times with those of appropriate reference compounds in the two chromatographic systems and (ii) by comparison of their mass spectra with those of reference compounds. These retinoids were: 13-cis-4-oxoretinoic acid, all-trans-4-oxoretinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid, all-trans-retinoyl beta-glucuronide and all-trans-retinyl beta-glucuronide. One further metabolite could be identified for the first time as all-trans-4-oxoretinoyl beta-glucuronide by its mass spectrum and, after treatment of the unknown metabolite with beta-glucuronidase, by its hydrolysis product all-trans-4-oxoretinoic acid. The molecular structure of one metabolite could not be elucidated. A major metabolic pathway of high-dose vitamin A in the non-human primate is apparently the oxidation of the primary alcohol group of retinol resulting in the formation of all-trans-retinoic acid. Subsequently, a broad spectrum of various metabolites of all-trans-retinoic acid, including beta-glucuronides and retinoids with a 13-cis configuration, appear in the plasma.
 ...
PMID:Characterization of oxidized and glucuronidated metabolites of retinol in monkey plasma by thermospray liquid chromatography/mass spectrometry. 240 Aug 53

Administration of a single oral dose (10 micrograms/kg) of tetrachlorodibenzo-p-dioxin (TCDD) caused a 33% decrease in retinyl esters in the livers of male rats, but a 13-fold increase in retinyl esters in the kidney and a 3-fold increase in serum retinol. Liver and kidney microsomal uridine diphosphoglucuronosyltransferase (UDPGT) activity toward all-trans-retinoic acid was increased 3.7- and 2.6-fold, respectively, ten days following exposure to TCDD. Verification of the in vitro formation of [3H]retinoyl beta-glucuronide (RG) was by cochromatography with authenic RG on reversed phase high pressure liquid chromatography (HPLC), identification of retinoic acid as the hydrolysis product after beta-glucuronidase treatment, and the characterization of the all-trans-retinoyl glucuronide by negative fragment mass spectroscopy, fast atom bobardment. We conclude that increased retinoic acid glucuronidation may be a contributing factor to the hepatic depletion of vitamin A and the increased excretion of vitamin A metabolites following TCDD exposure.
 ...
PMID:Effect of tetrachlorodibenzo-p-dioxin (TCDD) on the glucuronidation of retinoic acid in the rat. 250 57

Retinyl beta-glucuronide has been identified as a normal endogenous component of human blood, as have retinoyl beta-glucuronide and retinoic acid. The mean serum concentration of retinyl beta-glucuronide in adult volunteers (n = 6) was 6.8 +/- 4.0 nmol/L (means +/- SD) with a range from 1 to 11 nmol/L. Purified serum retinyl beta-glucuronide was characterized by the mass spectrum of its methylated trimethylsilyl derivative, by its hydrolysis by beta-glucuronidase, and by its chromatographic behavior in high-performance liquid chromatography systems. During a single day, concentrations of retinyl beta-glucuronide, retinoyl beta-glucuronide, and retinoic acid varied approximately two-fold.
 ...
PMID:Characterization of retinyl beta-glucuronide in human blood. 275 24

Retinoic acid (0.5% in acetone) was applied topically to the back skin of five juvenile rhesus monkeys once a day for 7 successive days. Two control animals were given vehicle alone. Skin specimens were taken from each animal at 0, 1, 2, and 4 weeks. The tissues were prepared for both histology (1-micron plastic sections) and split epidermal sheets (after incubation with EDTA solution, 17 mM). The split epidermal sheets were stained with ATPase and anti-Ia antibody, and the number of Langerhans cells was counted. The activity of beta-glucuronidase in the split epidermis was assayed by Fishman's method. After one week of treatment, the epidermis showed marked acanthosis and hyperkeratosis. The Langerhans cells showed severe degeneration, and the number of cells had dropped to approximately one-third of the number in the control skins. Concomitantly, the activity of beta-glucuronidase in the epidermis had also decreased to one-third of the control levels. After withdrawal, the number of Langerhans cells and activity of beta-glucuronidase showed gradual recovery, and by the fourth week they were back to the ranges of pretreatment or control skins, but acanthotic change remained. The results suggest that retinoid applied topically to normal primate skin induces reversible degeneration and desquamation of the Langerhans cells, while the epidermis shows prolonged proliferative change.
 ...
PMID:Effects of retinoic acid on the epidermal Langerhans cells and beta-glucuronidase activity in macaque skin. 295 32

The occurrence of retinoyl beta-glucuronide and retinoic acid as normal endogenous components of vitamin A reserve in human blood has been demonstrated. Use of high-performance liquid chromatography, coupled with a sensitive detector and integrator, has enabled us to quantitate nanogram quantities of the two retinoids. Serum concentrations of retinoyl glucuronide and retinoic acid in all the volunteers studied ranged from 1.5 to 5.1 ng/ml (mean 2.42 ng/ml) and from 1.0 to 3.2 ng/ml (mean 1.80 ng/ml) serum, respectively. The identity of retinoyl beta-glucuronide was confirmed by its conversion to retinoic acid by the action of beta-glucuronidase and by study of the mass spectrum of the methylated derivative.
 ...
PMID:Retinoyl beta-glucuronide: an endogenous compound of human blood. 396

12-O-Tetradecanoylphorbol 13-acetate (TPA), phorbol 12,13-diacetate and phorbol 12,13-didecanoate were all potent inducers of thromboplastin activity in human monocytes in vitro, whereas 4 alpha-phorbol 12,13-didecanoate and 4 alpha-phorbol had no such effect. A concomitant increase in titrable apoprotein III antigen was found (apoprotein III is the protein component of thromboplastin). The increase was inhibited by cycloheximide and actinomycin D and partly by alpha-amanitin. The increase of thromboplastin activity was therefore most likely due to synthesis de novo of apoprotein III. The response was approximately halved in the absence of serum or Ca2+. Retinol had a weak inhibitory effect, and retinoic acid was inhibitory only at concentrations that also induced signs of cytotoxicity. TPA caused an initial rise in monocyte cyclic AMP concentration of about 90-120 min duration. No increase in 45Ca2+ influx was induced over 2 h. Good correlation exists between induction of apoprotein III synthesis in monocytes in vitro and mouse skin-tumour promotion in vivo by the various phorbol derivatives. Substances inactive in tumour promotion do not induce the synthesis of apoprotein III. General activating and cytotoxic effects of TPA were monitored by determining release of lysozyme, beta-glucuronidase and lactate dehydrogenase.
 ...
PMID:Phorbol esters induce synthesis of thromboplastin activity in human monocytes. 627 36

The major metabolite in the small intestinal mucosa of vitamin A deficient rats dosed intrajugularly with 5,6-epoxy[3H]-retinoic acid has been identified as 5,6-epoxyretinoyl beta-glucuronide. The assignment was based on the metabolite's chemical, spectral, and chromatographic properties. Incubation of the metabolite with beta-glucuronidase released 5,6-epoxyretinoic acid. Incubation of 5,6-epoxyretinoic acid with rat liver microsomes in the presence of uridine-5'-diphospho-1 alpha-D-glucuronic acid produced the metabolite. 5,6-Epoxy[3H]retinoyl beta-glucuronide weas observed in the liver, small intestinal mucosa, and intestinal contents but not in kidney of vitamin a deficient rats. Its concentration was greatly diminished in liver and small intestinal mucosa, and it was not observed in kidney of vitamin A deficient rats dosed orally with retinoic acid for several days before administration of 5,6-epoxy[3H]retinoic acid. Generally, oral retinoic acid treatment accelerated 5,6-epoxyretinoic acid metabolism and enhanced accumulation of highly polar metabolites. Moreover, 5,6-epoxyretinoic acid metabolism was more rapid than that of retinoic acid and did not result in production of retinoic acid.
 ...
PMID:Metabolism of 5,6-epoxyretinoic acid in vivo: isolation of a major intestinal metabolite. 708 54

The biochemical basis for the cancer chemopreventive and anti-cancer activities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Neither alone nor in combination did these agents affect the level in the rat, of enzymes which are (a) known to correlate with reduced risk of carcinogenesis (detoxification enzyme, catalase, glutathione reductase) nor (b) enzymes which correlate with increased risk of carcinogenesis (beta-glucuronidase, xanthine oxidase, glucose-6-phosphate dehydrogenase). Retinoids, but neither glucarate nor its lactone inhibited free radical-induced lipid peroxidation. Both agents alone and synergistically in combination, raise cellular cAMP levels, repress protein kinase C and more generally inhibited DNA synthesis.
 ...
PMID:Basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination. 851 53


1 2 Next >>