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 presence of a pinocytosis receptor, specific for mannose-fucose terminated glycoproteins, has been established on murine resident peritoneal macrophages, thioglycollate-elicited peritoneal macrophages, and macrophages derived from bone-marrow in culture. Macrophagelike cell lines (J-774 and P338.D1), a myelomonocytic cell line (427E), lymphocytes, polymorphonuclear leukocytes, and fibroblasts were negative. Binding and uptake of 125I-mannose-BSA and 125I-beta-glucuronidase, respectively, into thioglycollate-induced peritoneal macrophages is saturable (Kd 4 degrees C = 5.4 X 10(-9) M; Kuptake 37 degrees C = 7 X 10(-7) M) and sugar specific. Macrophage-macrophage (rat X mouse) hybrids prepared by fusing rat alveolar macrophages with J-774-B10 (HAT-sensitive macrophagelike cell line) expresses the mannose-fucose receptor. Karyotypes of the hybrids confirmed a 1:1 fusion of rat and mouse cells. The rat/mouse hybrids express a variety of rat and mouse antigens including Fc receptors. Fibroblast-macrophage hybrids and melanoma-macrophage hybrids were negative for mannose-fucose receptor activity. The expression of the mannose-fucose receptor by macrophages appears to be regulated independently of other macrophage markers.
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PMID:Expression of a mannosyl-fucosyl receptor for endocytosis on cultured primary macrophages and their hybrids. 627 73

It has previously been shown that enzymatically hydrolyzed urine of patients with malignant melanoma contains 5,6-dihydroxyindole (5, 6DHI ). In this study we describe the elucidation of the entire structure of urinary 5, 6DHI -conjugate. Differential hydrolysis of melanotic urine revealed that, in contrast to beta-glucuronidase, sulfatase can liberate 5, 6DHI from its conjugated form. 5, 6DHI -sulfate was synthetized by reacting 5, 6DHI with sulfur trioxide trimethylamine complex. Thin-layer chromatography (TLC) documented its close similarity to the Thorm ahlen -positive compound usually entitled "C." Gas chromatographic-mass spectrometric (GC-MS) analysis of methylated and subsequently hydrolyzed synthetic 5, 6DHI -sulfate showed that the synthetic product consisted of a mixture of 5-hydroxy-6-indolyl-O-sulfate and 6-hydroxy-5-indolyl-O-sulfate (with a certain amount of 5, 6DHI -disulfate). 5, 6DHI -sulfate was purified with use of DEAE-cellulose column chromatography from melanotic urine. Methylation of this conjugate with deuterated dimethylsulfate and subsequent GC-MS analysis of the hydrolyzed product provided evidence that 5, 6DHI from melanotic urine was almost exclusively sulfated in position 6. It was concluded (1) that 5, 6DHI is excreted as a 6-O-sulfate, and (2) that this compound is consistent with Thorm ahlen -positive compound "C".
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PMID:Identification of 5-hydroxy-6-indolyl-O-sulfate in urine of patients with malignant melanoma. 654 57

Heparan sulfate (HS), a prominent component of vascular endothelial basal lamina, is cleaved into large Mr fragments and solubilized from subendothelial basal lamina-like matrix by metastatic murine B16 melanoma cells. We have examined the degradation products of HS and other purified glycosaminoglycans produced by B16 cells. Glycosaminoglycans 3H-labeled at their reducing termini or metabolically labeled with [35S]sulfate were incubated with B16 cell extracts in the absence or presence of D-saccharic acid 1,4-lactone, a potent exo-beta-glucuronidase inhibitor, and glycosaminoglycan fragments were analyzed by high speed gel permeation chromatography. HS isolated from bovine lung, Engelbreth-Holm-Swarm sarcoma, and subendothelial matrix were degraded into fragments of characteristic Mr, in contrast to hyaluronic acid, chondroitin 6-sulfate, chondroitin 4-sulfate, dermatan sulfate, keratan sulfate, and heparin which were essentially undegraded. Heparin, but not other glycosaminoglycans, inhibited HS degradation. The time dependence of HS degradation into particular Mr fragments indicated that HS was cleaved at specific intrachain sites. In order to determine specific HS cleavage points, HS prereduced with NaBH4 was incubated with a B16 cell extract and HS fragments were separated. The newly formed reducing termini of HS fragments were then reduced with NaB[3H]4, and the fragments hydrolyzed to monosaccharides by trifluoroacetic acid treatment and nitrous acid deamination. Since 3H-reduced terminal monosaccharides from HS fragments were overwhelmingly (greater than 90%) L-gulonic acid, the HS-degrading enzyme responsible is an endoglucuronidase (heparanase).
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PMID:Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase. 669 65

We measured free and total 5-S-cysteinyldopa excretion in 24-h urine specimens from nine patients with malignant melanoma and forty-five controls, and found that the levels of 5-S-cysteinyldopa excretion (measured by a fluorometric method) were greatly increased in the melanoma patients. The conjugates were hydrolysed by enzymatic treatment with beta-glucuronidase/arylsulphatase, and we found that the percentage of conjugated 5-S-cysteinyldopa was higher in urines with a low content of free 5-S-cysteinyldopa than in those with a higher concentration.
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PMID:Urinary free and conjugated 5-S-cysteinyldopa in normal subjects and in patients with melanoma. 680 Mar 94

The clinical findings and response to treatment of leptomeningeal metastases from solid tumors are analyzed in 90 patients treated at Memorial Sloan-Kettering Cancer Center during the period from January 1975 to February 1980. Patients included those who had either typical clinical findings of leptomeningeal tumor or conclusive laboratory evidence supporting the diagnosis. Carcinoma of the breast (46 patients), lung (23 patients) and melanoma (11 patients) were the common primary tumors. Symptoms of leptomeningeal metastasis occurred as the presenting sign in five patients and as late as ten years after the primary tumor was diagnosed in four other patients. Most patients had active systemic disease outside the nervous system. Signs and symptoms could be classified as involving either the brain, cranial nerves, or spinal nerves. Most patients had either symptoms or signs in more than one area at the time the diagnosis was established. The initial spinal fluid examination was abnormal in all but three patients, but only 49 had cytologic evidence of leptomeningeal metastases. Repeated spinal fluid assay yielded a positive cytology in 82 patients. Measurement of biochemical markers, including beta-glucuronidase, carcinoembryonic antigen and lactic dehydrogenase, assisted in the diagnosis. Approximately half of the patients treated by intraventricular methotrexate experienced improvement or stabilization of neurological symptoms for more than a month; median survival was 5.8 months after diagnosis, with a range of 1--29 months. In 18 patients disease was limited to the nervous system, and median survival was eight months, with four patients surviving one year and two patients for two years. Side effects of therapy were, for the most part, minor. We conclude that vigorous treatment of leptomeningeal metastases with intrathecal chemotherapeutic agents improves symptomatology in some patients, and at times prolongs survival.
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PMID:Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. 689 13

In solid s.c. tumors of a variant of the murine B16 melanoma with high metastatic potential (B16F10), there was a 2- to 7-fold elevation of lysosomal cathepsin B activity when compared to the B16F1 variant with low metastatic potential. The highest activities (based on either protein or DNA) of cathepsin B were found in tumors of less than 1 g. When B16F1 and B16F10 melanoma variants were grown in tissue culture, the metastatic differential in cathepsin B activity was lost as the cells were subcultured. However, this differential in cathepsin B activity could be restored by reestablishing the cultured cells as s.c. tumors. The activities of four other lysosomal enzymes (cathepsin D, beta-N-acetylglucosaminidase, beta-glucuronidase, and acid phosphatase) showed little evidence of a positive correlation with the metastatic potential of the B16 melanoma variants. Eighty to 90% of cathepsin B activity has been localized to a fraction containing viable tumor cells which was isolated by centrifugal elutriation. In contrast, only 50% of cathepsin D activity was in the viable tumor cell fraction, and from 30 to 70% of beta-N-acetylglucosaminidase, beta-glucuronidase, and acid phosphatase. Elevated levels of cathepsin B in the high metastatic B16F10 variant are consistent with the idea that cathepsin B may play a direct or a regulatory role in tumor metastasis.
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PMID:Cathepsin B activity in B16 melanoma cells: a possible marker for metastatic potential. 705 93

Lactic dehydrogenase (LDH) isoenzymes were measured in the cerebrospinal fluid (CSF) patients suffering a variety of cancer-related neurologic problems. LDH-5 isoenzyme as a percentage of total LDH activity was abnormally elevated (above 10 to 15%) in leptomeningeal infiltration by carcinoma (breast carcinoma, lung carcinoma, and malignant melanoma) but not in other types of CNS metastases. Abnormal LDH isoenzyme patterns were also seen with CSF infections in which a granulocytic pleocytosis was present. In the absence of infection, an elevated LDH isoenzyme 5:1 ratio suggested leptomeningeal tumor and, when used with other CSF markers (beta-glucuronidase and CEA), LDH, isoenzymes aid in early detection of this metastatic neoplastic process. They may also help to differentiate leptomeningeal tumor from other chronic meningitides. Measurement of CSF markers also aids in assessing the effectiveness of treatment since marker levels often vary with the clinical course.
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PMID:Lactic dehydrogenase isoenzymes in the cerebrospinal fluid of patients with systemic cancer. 726 Aug 57

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

Hypoxoside is the major diglucoside isolated from the corms of the plant family Hypoxidaceae. It contains an unusual E-pent-1-en-4-yne 5-carbon bridging unit with two distal catechol groups to which the glucose moieties are attached. It is non-toxic for BL6 mouse melanoma cells in tissue culture on condition that the fetal calf serum in the medium is heat-inactivated for 1 hour at 56 degrees C in order to destroy endogenous beta-glucosidase activity. The latter catalyses hypoxoside conversion to its cytotoxic aglucone, rooperol, which, when tested as a pure chemical, caused 50% inhibition of BL6 melanoma cell growth at 10 micrograms/ml. Light and electron microscopy revealed that the cytotoxic effect of rooperol manifested as vacuolisation of the cytoplasm and formation of pores in the plasma membrane. Indications of apoptosis were also found. Pharmacokinetic studies on mice dosed intragastrically with hypoxoside showed that it was deconjugated by bacterial beta-glucosidase to form rooperol in the colon. Surprisingly, no hypoxoside or rooperol was detectable in the serum. Only phase II biotransformation products (sulphates and glucuronides) were present in the portal blood and bile. In contrast, however, in human serum after oral ingestion of hypoxoside, the metabolites can reach relatively high concentrations. Rooperol metabolites isolated from human urine were non-toxic for BL6 melanoma cells in culture up to a concentration of 200 micrograms/ml. In the presence of beta-glucuronidase, which released rooperol from the metabolites, 50% growth inhibition was achieved at a 75 micrograms/ml metabolite concentration. The supernatant of a human melanoma homogenate could also cause deconjugation of the metabolites to form rooperol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphological characterisation of the cell-growth inhibitory activity of rooperol and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy. 854 43

The antimetastatic activity of ten compounds structurally related to nojirimycin A was examined using a pulmonary metastatic model of mouse B16 melanoma. Nojirimycin B, deoxynojirimycin, D-gluco-delta-lactam, CP3068 and CP3069 are structural analogues of nojirimycin A, and showed potent or moderate antimetastatic activities. Nojirimycin A, nojirimycin B, deoxynojirimycin and D-gluco-delta-lactam showed potent or moderate inhibitory activities against alpha-glucosidase, beta-glucosidase and beta-mannosidase, but CP3068 and CP3069 in which the structures were related to D-gluco-delta-lactam showed no inhibitory activities. CP3041, CP3042, CP3043, CP3045 and CP3048 are analogues of sodium D-glucaro-delta-lactam (ND2001), a carboxy derivative of nojirimycin A, and showed potent or moderate antimetastatic activities. But no analogue was superior to ND2001 concerning with antimetastatic and anti-beta-glucuronidase activities. CP3041 and CP3042 showed potent and moderate inhibitory activities against beta-glucuronidase, respectively, but CP3043, CP3045 and CP3048 showed little or no activities.
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PMID:Inhibition of mouse tumor metastasis with nojirimycin-related compounds. 862 56


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