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 pluripotent human erythroleukaemia cell line, HEL, possesses erythrocytic, megakaryocytic and macrophage-like properties. With respect to signal transduction, HEL cells have been used as a model system for platelets, but little attention has been paid to their phagocytic properties. We studied the effects of various receptor agonists on the intracellular free Ca2+ concentration ([Ca2+]i) in HEL cells. Thrombin, platelet-activating factor (PAF), ATP, UTP, prostaglandins E1 and E2 (PGE1 and PGE2), the PGE2 analogue sulprostone and the stable PGI2 analogues iloprost and cicaprost increased [Ca2+]i. ADP was less effective than ATP, and UDP was unable to increase [Ca2+]i. The increases in [Ca2+]i induced by thrombin, PAF, ATP, UTP, iloprost and cicaprost were pertussis toxin-insensitive, whereas the increases induced by PGE2 and sulprostone were completely inhibited by the toxin. The increase in [Ca2+]i induced by PGE1 was partially inhibited by pertussis toxin. PGE2 did not desensitize the increase in [Ca2+]i induced by iloprost, and vice versa. PGE1 desensitized the response to PGE2 and iloprost but not vice versa. Adrenaline potentiated the iloprost- but not the PGE2-induced rise in [Ca2+]i. The phorbol ester phorbol 12-myristate 13-acetate completely blocked the rise in [Ca2+]i induced by ATP and PGE1, whereas the increases induced by thrombin and PAF were only partially inhibited. Agonists increased [Ca2+]i through release from internal stores and sustained Ca2+ influx. Thrombin stimulated Mn2+ influx, which was blocked by Ni2+. Diltiazem, isradipine, gramicidin and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365) did not affect agonist-induced rises in [Ca2+]i. HEL cells contained substantial amounts of beta-glucuronidase which, however, could not be released, and they did not aggregate or generate superoxide. Our data suggest that: (1) HEL cells possess nucleotide receptors with properties similar to those of phagocytes; (2) they possess receptors for PGE2 and PGI2, and PGE1 is an agonist at both receptors; (3) agonist-induced increases in [Ca2+]i are mediated through pertussis toxin-sensitive as well as -insensitive signal transduction pathways; and (4) agonists increase [Ca2+]i by mobilization from internal stores and influx from the extracellular space through cation channels with properties similar to those of phagocytes and platelets.
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PMID:Receptor-mediated increases in cytosolic Ca2+ in the human erythroleukaemia cell line involve pertussis toxin-sensitive and -insensitive pathways. 131 May 89

The effect of various metals on uridine diphosphate (UDP)-glucuronyltransferase and beta-glucuronidase activities in rat liver microsomes was investigated. The presence of Mn2+, Cd2+, Zn2+, V5+, Ni2+, Co2+, Cu+ or Ca2+ (20 microM) in the enzyme reaction mixture did not cause a significant alteration of UDP-glucuronyltransferase activity in hepatic microsomes. Of these metals, Zn2+ and Cd2+ (20 microM) caused a remarkable increase in hepatic microsomal beta-glucuronidase activity. Appreciable effects of Zn2+ and Cd2+ on beta-glucuronidase activity were seen at 5.0 microM, and the effects were saturated at 50 microM. Ca2+ (5.0-50 microM) and/or the Ca2(+)-binding protein regucalcin (2.0 microM) did not have an appreciable effect on UDP-glucuronyltransferase and beta-glucuronidase activities in hepatic microsomes. Thus, Zn2+ and Cd2+ uniquely increased beta-glucuronidase activity. The Zn2(+)- and Cd2(+)-induced increase in beta-glucuronidase activity was completely reversed by the presence of an SH group-protecting reagent (dithiothreitol). The response of the microsomal enzyme to Zn2+ and Cd2+ (20 microM) was no longer seen after treatment with 0.2% Triton X-100 [polyoxyethylene(10)octylphenyl ether], indicating that the stimulation by these metals is dependent on membrane association. The present study suggests that, of various metals tested, Zn2+ and Cd2+ can uniquely increase hepatic microsomal beta-glucuronidase activity and that their effect is based on binding to membranous SH groups, beside the enzyme protein.
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PMID:Effects of Ca2+, Zn2+ and Cd2+ on uridine diphosphate-glucuronyltransferase and beta-glucuronidase activities in rat liver microsomes. 211 Aug 67

Nickel subsulfide (Ni3S2), nickel sulfate (NiSO4), and nickel oxide (NiO) are encountered occupationally in the nickel refining and electroplating industries, with inhalation being a common route of exposure. The purposes of this study were to evaluate the biochemical responses of lungs of rats and mice exposed for 13 weeks to occupationally relevant aerosol concentrations of Ni3S2, NiSO4, and NiO, to correlate biochemical responses with histopathologic changes, and to rank the compounds by toxicity. Biochemical responses were measured in bronchoalveolar lavage fluid (BALF) recovered from lungs of exposed animals. Parameters evaluated in BALF were lactate dehydrogenase (LDH), beta-glucuronidase (BG), and total protein (TP). Total and differential cell counts were performed on cells recovered in BALF. All compounds produced an increase in LDH, BG, TP, and total nucleated cells, and an influx of neutrophils, indicating the presence of a cytotoxic and inflammatory response in the lungs of exposed rats and mice. Increases in BG were greater than increases in LDH and TP for both rats and mice. Chronic active inflammation, macrophage hyperplasia, and interstitial phagocytic cell infiltrates were observed histologically in rats and mice exposed to all compounds. Statistically significant increases in BG, TP, neutrophils, and macrophages correlated well with the degree of chronic active inflammation. Results indicated a toxicity ranking of NiSO4 greater than Ni3S2 greater than NiO, based on toxicities of the compounds at equivalent mg Ni/m3 exposure concentrations.
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PMID:Biochemical responses of rat and mouse lung to inhaled nickel compounds. 275 27

Guinea pig skin was treated with 50 mg/kg sodium lauryl sulphate (SLS) and nickel (Ni) alone and in combination (50 mg/kg SLS and 50 mg/kg Ni) for 7 and 14 days. Release of acid phosphatase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, beta-glucuronidase, lactic dehydrogenase and malic dehydrogenase was observed, following treatment with SLS and Ni alone or in combination. Similarly, the skin contents of amino nitrogen and sulphydryl groups also increased significantly. These alterations were slightly more marked when the skin was treated simultaneously with the combination of SLS and Ni. The present study suggests that industrial workers or populations exposed simultaneously to SLS and Ni are more prone to dermal irritation or inflammation.
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PMID:Effect of sodium lauryl sulphate and nickel alone and in combination on the skin of guinea pigs. 317 54

Rats and rabbits were exposed through the respiratory system to industrial dusts (magnesite emissions, solid wastes from nickel refinery dump, cement emissions) at biomonitory stations or in experimental chamber. Following exposure the animals were killed, the alveolar macrophages isolated and acid phosphatase and beta-glucuronidase estimated in the isolated cells. The activity of both enzymes was enhanced in the exposed animals in all cases. The enhancement was dependent on the length of exposure and amount of inhaled particles.
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PMID:Biomonitoring of industrial dusts on animals. II. Bioindication on alveolar macrophages. 364 12

Nickel subsulfide (Ni3S2), nickel chloride (NiCl2), nickel sulfate (NiSO4), and nickel oxide (NiO) are compounds of widely differing solubility encountered in the nickel-refining and electroplating industries. Inhalation is a common route of exposure and toxicity to the respiratory tract is possible. The purpose of this study was to evaluate the biochemical, cytological, and morphological changes in lung following administration of these compounds by intratracheal instillation. F344/Crl rats were administered a single dose of nickel compound containing 0.0, 0.01, 0.10, or 1.0 mumol Ni by intratracheal instillation. Rats were sacrificed at 1 or 7 days after compound administration, with half the animals in each exposure group taken for determination of nickel lung burden and the remaining half used for evaluation of biochemical, cytological, and histological changes. In the latter group, the right lung was lavaged and the fluid obtained was analyzed for indicators of pulmonary inflammation: lactate dehydrogenase (LDH), beta-glucuronidase (BG), total protein (TP), glutathione reductase (GR), glutathione peroxidase (GP), and sialic acid (SA). Total and differential cell counts on cells recovered in lavage fluid were also determined. The left lobe was examined for morphological changes. Clearance of nickel from the lung was most rapid for NiCl2 and NiSO4, followed by Ni3S2 and NiO. Minimal changes in all parameters were observed at 1 day after exposure. No significant changes in any parameter occurred in rats exposed to NiO, while Ni3S2, NiSO4, and NiCl2 caused increased in LDH, BG, TP, GR, SA, and total nucleated cells at 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative acute toxicity of four nickel compounds to F344 rat lung. 375 51

The metabolism of endogenous estrogens, estradiol and estrone, and the irreversible binding of estrogens to cellular macromolecules have been examined and compared in subcellular microsomal and in intact hepatocyte preparations. In studies with rat liver microsomal preparations containing estradiol, an NADPH-generating system, and denatured DNA, the irreversible binding of radiolabeled steroid metabolite(s) to the microsomal proteins was 3.26 nmoles/mg protein in 1 hr (S.D. 0.39; 7.9% of total steroid) while binding to DNA was found to be 0.288 nmole/mg DNA/mg protein (S.D. 0.025; 0.39% of total steroid). No significant difference was observed between microsomal preparations from untreated, phenobarbital-treated or 3-methylcholanthrene-treated rats. Irreversible binding to proteins was also demonstrated in the intact hepatocyte cell incubations. After 2-hr incubations of estradiol with hepatocytes, 5.9% (S.D. 1.4%) of the steroid(s) was irreversibly associated with cellular proteins (approximately 1.43 pmoles/mg/min). Analysis of the organic-soluble metabolites demonstrated the presence of the catechol estrogens and their metabolites, 2-hydroxyestradiol, 2-hydroxyestrone, 2-methoxyestradiol, and 2-methoxyestrone. Estrone and estriol were also identified. The aqueous-soluble materials isolated from hepatocyte incubations contained glucuronide, sulfate, and apparent thioether conjugates, as determined by liberation from estrogen metabolites by treatment with beta-glucuronidase, sulfatase, and Raney nickel. Thus, extensive primary and secondary metabolism of estrogens occurs in intact hepatocyte incubations. Furthermore, irreversible binding of estrogens to cellular proteins occurs in these intact cells having demonstrated conjugative pathways of metabolism.
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PMID:Estrogen metabolism in rat liver microsomal and isolated hepatocyte preparations--I. Metabolite formation and irreversible binding to cellular macromolecules. 650 37

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

Rats were exposed to nickel sulfate (NiSO4) either by intratracheal (IT) instillation or by acute aerosol inhalation, and pulmonary clearance of Ni and pulmonary inflammatory responses were studied. The half-time of Ni in the lung (initial lung burden = 50 micrograms Ni/rat) was about 32 h in both the IT instillation and inhalation groups. Ni retention in the lung tissue following IT instillation of NiSO4 was saturable with reference to dose, suggesting that clearance rate of Ni from the rat lung depends on lung burden of Ni. Lung inflammatory responses were evaluated by biochemical, elemental and cytological indicators in bronchoalveolar lavage fluid (BALF) following IT instillation of NiSO4. Activities of lactate dehydrogenase and beta-glucuronidase, contents of lysozyme, protein, sulfur and calcium, and the number of polymorphonuclear leukocytes were increased with a peak at 2-3 days post-instillation, while BALF alkaline phosphatase (ALP) activity was significantly decreased after IT instillation of NiSO4. Lung tissue ALP activity was also decreased by NiSO4. Because Ni does not inhibit ALP directly, the decrease in ALP activity is probably due to functional changes of type II cells (a major source of BALF ALP). Thiobarbituric acid reacting substances in the lung tissue were not changed by NiSO4, suggesting that lipid peroxidation plays a minimal, if any role, in the Ni-induced inflammation in the rat lung.
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PMID:Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats. 799 20

The aim of this investigation was to assess the cytotoxic effect of nickel hydroxy carbonate (NiHC) on guinea pig alveolar macrophages (AMs) by studying ultrastructural modifications and by determining beta-glucuronidase (BG) and lactate dehydrogenase (LDH) activities, as well as cellular ATP content. The ultrastructural studies revealed phagocytosis of NiHC particles and a general vacuolisation of the cells, especially at high concentrations. X-ray microprobe analyses of these particles demonstrated the presence of Ni, P and Ca which suggests the formation of Ni-P-Ca complexes. In exposed cells, a biphasic change in intracellular ATP concentrations was observed which could indicate 'activation' of AMs at low concentrations and inhibition of energy generation at higher concentrations. As for enzymatic activities, a dose-dependent increase in LDH release was observed except at low doses which increased ATP. There was a good correlation between ATP decrease and LDH release, consistent with a dose-dependent cytotoxic effect of NiHC. However beta-glucuronidase activity remained unchanged at all NiHC concentrations. It has been concluded that NiHC undergoes an intracellular, biological transformation to form Ni-P-Ca. Further investigations are needed to determine the precise nature and importance of these complexes.
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PMID:Ultrastructural and biochemical changes in alveolar macrophages exposed to nickel hydroxy carbonate. 802 93


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