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 histochemistry of armadillo skin has been studied. The dendritic cells are extremely large, very sharply outlined by methods for alkaline phosphatase and alpha-naphthyl-acetate esterase, and they are dopa-negative. The mastocytes, however, are dopa-oxidase-positive, probably due to peroxidase rather than tyrosinase activity. The giant cells of the granulomas normally seen in the dermis of the armadillo are strongly beta-glucuronidase-positive. These giant cells are evidently foreign body cells reacting to the crystals always present in the dermis of the armadillo. The centre of these crystals, which are cholesterol and fat-negative, is alkaline phosphatase-positive. Further study of the mastocytes and dendritic cells is necessary to elucidate their nature.
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PMID:The histochemistry of armadillo skin. 81 35

The dermal cells in grey, xanthic, and white goldfish integuments were cytochemically characterized for the following enzymatic activities: tyrosinase, DOPA-oxidase, cytochrome oxidase, monoamine oxidase, peroxidase, non-specific esterase, cholinesterase, NAD-diaphorase, NADP-diaphorase, aryl sulfatase, nucleotide phosphodiesterase, beta-glucuronidase, acid phosphatase, alkaline phosphatase, adenosine triphosphatase, thiamine pyrophosphatase, glucose-6-phosphatase, aldolase, as well as succinate, malate, isocitrate, glutamate, glucose-6-phosphate, 6-phosphogluconate, alpha-glycerophosphate, alcohol, lactate, and beta-hydroxybutyrate dehydrogenases. It was found that the epidermis was a significant barrier to the access of cytochemical reaction substrates. Removal of the epidermal barrier provided dermal cell localizations of enzymatic activities which were reproducible. Further, alterations in reaction times and temperatures from the mammalian methodology provided conditions fe various integumental cells were compared for possible interrelationships. The basic foundations for future work with the dermis of poikilothermic vertebrates on an experimental basis were established. In addition, a previously undescribed non-pigmented dermal cell, the "x"-cell, was found to have enzymatic characteristics similar to both melanophores and lipophores. The "x"-cell may be the common precursor of both types of pigment cells.
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PMID:Cytochemical characterization of goldfish (Carassius auratus L.) dermis with special reference to the pigment cells. 82 86

The guinea pigs were dermally exposed to paraphenylenediamine (PPD) and in presence of an oxidising agent hydrogen peroxide for 15 and 30 d to assess their effects on some enzymes, lipid peroxidation and histamine contents in the skin. The activities of acid and alkaline phosphatases, beta-glucuronidase, gamma glutamyl transpeptidase, histidase and tyrosinase were enhanced after application of either PPD or PPD plus hydrogen peroxide. The lipid peroxidation and histamine contents also showed marked elevation following exposure to the chemicals.
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PMID:Dermal toxicity of paraphenylenediamine. 148 26

The skins of guinea pigs were exposed to 50 mg/kg hexachlorophene (HCP) for 7, 15 or 30 days. The activities of skin marker enzymes (beta-glucuronidase, histidase, tyrosinase) increased, but glutathione decreased. Lipid peroxidation and histamine contents increased during different time intervals. The histopathological changes showed damage to epidermis and dermis. Depending on the duration of exposure, HCP produces biochemical and histopathological damage to skin.
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PMID:Dermal exposure of hexachlorophene to guinea pigs. 162 61

A spontaneous, hypomelanotic variant (MI) of the highly melanotic transplantable hamster melanoma of Bomirski (Ma) is the subject of this report. Tyrosinase activity is 2-3 times higher, but melanin content significantly lower than in the parental Ma melanotic melanoma. Acid phosphatase activity is similar in both, but beta-glucuronidase and aryl-sulfatase A are 2-3 times higher in the hypomelanotic variant. Transplanted MI melanomas grow more slowly than the parental tumor, but metastasize with similar incidence and localization. Hypomelanotic variant melanoma cells, even those in grossly nonnecrotic parts of the transplants, show signs of low viability like swelling of the cytoplasm or cellular condensation, and disintegration. Autophagic vacuoles are numerous. They appear to be formed by enclosure of a portion of cytoplasm by cisternae of smooth endoplasmic reticulum or trans-Golgi network. These limiting cisternae contain tyrosinase as evidenced by deposition of electron dense reaction product on incubation with tyrosine or DOPA. Other sites of ultrastructural tyrosinase reaction are melanosomes and the smooth-surfaced cisternae and vesicles of the trans-Golgi network. We postulate the low cell viability, associated with autophagosome formation, is the cause for the growth retardation of the MI variant, and that the lower melanin content of these tyrosinase-rich cells is due to sequestration of a substantial portion of newly synthesized enzyme into autophagic vacuoles before it has the chance of being incorporated into melanosomes.
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PMID:Pathology and ultrastructural characteristics of a hypomelanotic variant of transplantable hamster melanoma with elevated tyrosinase activity. 311 4

Using two sources of selection, the higher beta-glucuronidase and tyrosinase content of malignant melanomas, new transport forms are synthetized, which are toxified to quinoids, cytotoxic products by the above mentioned enzymes. These transport forms selectively inhibit the growth of melanomas. For instance, 4-methylcatechol-2-O-beta-D-glucopyranosiduronic acid (3) is synthetized by the reaction of 4-methylcatechol with tetra-O-acetyl-beta-D-glucopyranosiduronic acid methyl ester in the presence of p-toluenesulfonic acid following treatment with alkali. 3 inhibits the growth of B16 melanoma of the mouse significantly.
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PMID:[Synthesis and melanoma inhibiting properties of 4-alkylpyrocatechol-2-O-beta-D-glucopyranosiduronic acids and their esters]. 323 38

Melanosomes, the subcellular site of melanin synthesis and deposition, may be related to the endolysosomal lineage of organelles. To determine if melanosomes contain lysosomal hydrolases, we examined the subcellular distribution of five of these enzymes in melanocytes cultured from C57BL/6J mice. Analyses of Percoll gradient density centrifugations demonstrated that beta-hexosaminidase, beta-galactosidase, beta-glucuronidase, and cathepsins B and L all co-sedimented with tyrosinase-rich densely sedimenting melanosomes. The melanosomal distribution of these enzymes was confirmed in studies of melanocytes cultured from albino mice and of melanocytes rendered amelanotic by transfection with the v-rasHa oncogene (which lack dense, melanized melanosomes). In these cells, only a less dense peak of activity for each hydrolase was present. The level of each hydrolase was elevated in black cells when compared with albino cells. Metabolic labeling studies confirmed that the increase in beta-glucuronidase in black versus albino cells resulted mainly from increased synthesis of this enzyme. The data suggest that melanosomes represent specialized lysosomes present within melanocytes, that they contain a broad array of lysosomal hydrolases, and that the levels of these hydrolases are elevated in cells actively engaged in pigment production.
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PMID:Lysosomal hydrolases are present in melanosomes and are elevated in melanizing cells. 787 79

Many genes mapping to pigmentation loci are involved in the regulation of melanin synthesis in the mouse. The brown (b) locus controls black/brown coat coloration, and its product has significant homology to the key melanogenic enzyme tyrosinase. This has led to suggestions that the b-protein is itself a melanogenic enzyme. In order to investigate its function, we have established lines of mouse fibroblasts stably expressing the b-protein by co-transfection of a b-protein expression vector and a plasmid conferring resistance to the antibiotic G418. The b-protein synthesised by these cells has the expected molecular mass of 75 kDa and reacts with three different anti-b-protein antibodies. We were unable to confirm previous reports that the b-protein has tyrosinase or catalase activity, but detected stereospecific dopachrome tautomerase activity in b-protein-expressing fibroblasts. This dopachrome tautomerase binds to Concanavalin A-Sepharose, and the major product of its action on L-dopachrome is 5,6-dihydroxyindole-2-carboxylic acid. Since this activity is not present in untransfected cells we conclude that the b-protein has dopachrome tautomerase activity. Fibroblasts do not contain melanosomes, the specialised organelles in which the b-protein is located in melanocytes. Nevertheless, indirect immunofluorescence localisation of the b-protein in transfected fibroblasts produces a distinctive pattern of intense juxtanuclear staining combined with punctate cytoplasmic staining. Double-labelling shows co-localisation of the b-protein with the late endosomal/lysosomal markers beta-glucuronidase and LAMP-1, both in transfected fibroblasts and in mouse melanoma cells. These findings are consistent with the hypothesis that melanosomes are closely related to lysosomes.
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PMID:The mouse brown (b) locus protein has dopachrome tautomerase activity and is located in lysosomes in transfected fibroblasts. 827 Jun 21

Melanomas exhibiting mutated ras genes are frequently invasive and amelanotic. Transfecting melanocytes with ras oncogenes causes transformation and a loss of visible pigmentation. We analyzed murine melanocytes rendered amelanotic by transfection with the v-rasHa oncogene. Consistent with previous reports, tyrosinase and tyrosinase-related protein-1 (TRP-1) were not expressed by transformed cells. In addition, lack of expression of TRP-2 and the product of the silver locus was documented. Levels of melanosomal matrix antigens, the pink-eyed dilution locus protein and lysosome-associated membrane protein-1 were markedly reduced. Residual matrix antigens were localized by immunofluorescence to large vacuoles distributed peri-nuclearly in transfected cells. Electron microscopy demonstrated the absence of typical melanosomes and the presence of large vacuolar structures, also in a peri-nuclear distribution. Although levels of lysosomal hydrolases, such as beta-glucuronidase and cathepsin D, were diminished, marked elevations were observed in the expression of cathepsins B and L, 2 thiol proteases implicated in the acquisition of invasiveness. Our data demonstrate that transfection of melanocytes with v-rasHa is sufficient to disrupt the biogenesis of melanosomes and to up-regulate thiol protease synthesis, providing insights into the amelanotic and invasive nature of melanomas exhibiting mutations in ras genes.
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PMID:Melanosomal and lysosomal alterations in murine melanocytes following transfection with the v-rasHa oncogene. 863 74

UV-mediated mutagenesis generated a high glucoamylase-producing mutant of Aspergillus oryzae exhibiting strong melanization in solid-state culture. Expression of the glucoamylase-encoding gene (glaB), which is specifically expressed in solid-state culture, and the tyrosinase-encoding gene (melO), was analyzed using an E. coli beta-glucuronidase (GUS) reporter assay to investigate this phenomenon. Although no common regulation was found for melO and glaB expression, the former was greatly enhanced in submerged culture. Interestingly, the melO promoter was about four times stronger for GUS production than the powerful promoters amyB, glaA, and modified agdA, previously isolated for industrial heterologous gene expression in A. oryzae. These findings indicated that the melO promoter would be suitable for hyper-production of heterologous protein in Aspergillus. The glaB-type glucoamylase selected as the target protein was produced in a submerged culture of A. oryzae under the control of the melO promoter. The maximum yield was 0.8 g/l broth, and the total extracellular protein purity was 99%. Repeated batch culture, to improve productivity, gave a maximum yield of 3.3 g/l broth. The importance of this work is in the establishment of a both high-level and high-purity protein overproduction system in A. oryzae by use of the melO promoter.
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PMID:Establishment of a hyper-protein production system in submerged Aspergillus oryzae culture under tyrosinase-encoding gene (melO) promoter control. 1169 10


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