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)

Auranofin (SK&F D-39162), a new antiarthritic gold compound reported to be orally effective in animal (adjuvant rat) and human (rheumatoid) arthritic conditions, is a potent in vitro inhibitor of the release of lysosomal enzymes from phagocytizing rat leukocytes. Auranofin, at micromolar concentrations (1-10 microM), produced a dose-dependent reduction in extracellular levels of lysosomal enzyme markers (beta-glucuronidase and lysozyme) which are selectively released from rat leukocytes during phagocytosis of zymosan particles. The reduction in extracellular levels of lysosomal enzymes appears to be caused by inhibition of their selective cellular release, since effective concentrations of auranofin did not produce leukocyte cytotoxicity or inhibition of cell-free lysosomal enzyme activity. Morphologic and biochemical evidence indicated that auranofin also interferes with phagocytosis of zymosan particles. The potent in vitro activity of auranofin appears to result from its unique gold complex, since neither structurally related nongold compounds nor clinically used gold compounds (gold sodium thiomalate and gold thioglucose) were potent inhibitors of lysosomal enzyme release. The results of this investigation suggest that the antiarthritic activity of auranofin may be caused at least in part, by inhibition of lysosomal enzyme release and/or cellular processing of antigens.
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PMID:Inhibition of lysosomal enzyme release from rat leukocytes by auranofin. A new chrysotherapeutic agent. 10 27

PVC dust, following a single intratracheal instillation (25 mg/rat), was substantially cleared through the lymphatic circulation and progressively accumulated in the tracheobronchial lymph nodes (TBLN) in a time-dependent manner for up to 1 year. The tissue response in TBLN during 60-270 days post-instillation of PVC dust was characterized by progressive increase in total organ fresh weight, dry weight, DNA, RNA and protein contents, concurrent with the proliferation of macrophages and hyperplasia of reticular cells. Active phagocytosis and enhanced hydrolytic activity in TBLN was evident around 270 days post-instillation by the appearance of PVC-laden macrophages near and within the dust foci, and increased activity of acid phosphatase, DNAse, RNAse and beta-glucuronidase. PVC dust caused degeneration of macrophages, and consequent release of hydrolytic enzymes resulted in limited cytotoxicity without inducing reticulination and fibrosis in the TBLN. The histology and clinical biochemistry of liver, kidney, spleen and serum were not altered and there were no detectable PVC particles in these tissues at up to 365 days. It is therefore concluded that lymphatic clearance of intratracheally instilled PVC dust results in its accumulation and mild foreign body reaction in TBLN which is non-fibrogenic at up to 365 days post-instillation.
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PMID:Pathobiochemical response of tracheobronchial lymph nodes following intratracheal instillation of polyvinylchloride dust in rats. 192 73

A method was developed for the analysis of non-reducing terminal structure of radiolabelled chondroitin sulphate chains with the aid of N-acetylgalactosamine 4-sulphatase ('terminal 4-sulphatase'), N-acetylgalactosamine 6-sulphatase ('terminal 6-sulphatase'), beta-glucuronidase and beta-N-acetylhexosaminidase. Studies with this method on the non-reducing terminal structure of [35S]sulphate- and [3H]glucose-labelled chondroitin sulphate chains from rat and chick-embryo cartilages showed that the presence of a high proportion of 4-sulphated hexosamine residues is a common feature of the termini of newly synthesized chondroitin sulphate chains. Of the non-reducing terminal 4-sulphated hexosamine residues, about 14% (chick embryo) or 46% (rat) contained an additional sulphate group at position 6. The internal portion of the chondroitin sulphate chains, in contrast, contained little or no 4,6-bis-sulphated hexosamine residue, suggesting that 4,6-bis-sulphated structure may play a role in biosynthetic control at the level of chain termination.
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PMID:A distinct terminal structure in newly synthesized chondroitin sulphate chains. 315 11

Adult male Fisher 344 rats (190-220 g), were given an intravenous dose (10 mg/rat) of BHA. Pretreated and control rats received an intravenous dose of [G-3H] acetaminophen (25 mg/rat). Bile was collected prior to dosing and for 5-6 hours after dosing at varying time intervals. Separate aliquots of 0.2 ml were incubated with beta-glucuronidase and sulfatase, respectively. These incubation mixtures were then extracted and analyzed by reverse phase HPLC. In all cases control animals showed a greater deceleration in the biliary excretion of the water soluble metabolites when compared with pretreated animals. Increases in both glucuronide and sulfate elimination processes are assumed to be contributory, in part, to the overall effect of BHA on acetaminophen metabolism.
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PMID:BHA (2(3)-tert-butyl-4-hydroxyanisole)-mediated modulation of acetaminophen phase II metabolism in vivo in Fisher 344 rats. 362 63

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

We compared in vivo biological effects, focusing on lung inflammatory responses after a single intratracheal administration of two types of well-characterized whiskers: potassium octatitanate and potassium hexatitanate, which have similar fiber sizes and chemical compositions, except their surface morphology. The geometrical mean of length (microm), width (microm), and geometric standard deviation (GSD) are: K(2)Ti(8)O(17) (PT1), 6.0[2.0], 0.35[1.51], having rough surface; K(2)Ti(6)O(13) (PT2), 5.0[2.18], 0.31[1.63], having smooth surface. Sixty male Wistar rats (8 wk old) under anesthesia were injected intratracheally with 2 doses of fibers (0.2 mg/0.5 ml/rat, 1.0 mg/0.5 ml/rat) or the same amount of saline solution (group C). Animals were sacrificed on days 1, 3, and 7 after fiber administration, and then the lung tissue and bronchoalveolar lavage (BAL) were collected. There were no obvious differences among the three groups in the yield of BAL fluid. Total protein concentration in BAL increased significantly from day 1; BAL fucose level increased significantly from day 3 in a dose-dependent manner, which gradually recovered by day 7 in groups PT1 and PT2. BAL total protein and fucose in group PT1 increased significantly compared with those in group PT2 at a dose level of 1.0 mg. A dose-independent increase of beta-glucuronidase activity and decrease of superoxide dismutase activity were observed in both fibers. BAL tumor necrosis factor-alpha (TNF-alpha) increased significantly in animals treated with 1.0 mg dosage of PT1 and PT2 on day 1. However, BAL IL-1beta did not show any marked change during the experimental period in animals treated with both fibers. On day 1, BAL cytokine-induced neutrophil attractants (CINC)/growth-related gene product (GRO) increased significantly in the PT1 group treated with 0.2 and 1.0 mg dosage. On day 3, the group treated with 1.0 mg PT1 showed significant increase of CINC/GRO compared with the group treated with 1.0 mg PT2, which recovered to the control level on day 7. Expression of various chemokine mRNAs (MCP-3, MIP-1alpha, RANTES, and eotaxin) increased in rats treated with PT1 or PT2 on day 1 and/or day 3. Increase of gene expression in the PT1 group was greater than that of the PT2 group at 0.2 mg dosage level. These results suggest that differences in the surface morphology of the whisker fibers of similar length and diameter, density, and chemical composition appear to be related to the facilitation of macrophage phagocytes in the macrophage-derived biological effects in acute lung injury induced by inhaled fibers.
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PMID:Effects of surface characteristics of potassium titanate whisker samples on acute lung injury induced by a single intratracheal administration in rats. 1202 5

It is known that RGS9-2 gene knockout mice show supersensitivity to DA and have a marked elevation in the proportion of DA D2 receptors in the high-affinity state for DA (D2(High) receptors). As this is a similar profile to that observed in the CNS from subjects with schizophrenia, we examined whether postmortem CNS tissue from subjects with the disorder and brain striata from an animal model of psychosis or schizophrenia (the amphetamine-sensitized rat) had altered levels of RGS9-2. The mRNA for RGS9-2 in 29 control hippocampi was 0.185 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), while that in 29 schizophrenia hippocampi was 0.145 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), a reduction of 22%. Of the many receptor-regulating genes related to G proteins, and of 11 RGS genes, RGS9-2 was the most reduced in the amphetamine-sensitized rat striatum. The reduced levels of RGS9-2 expression in both an animal model of schizophrenia and a postmortem schizophrenia brain provide further evidence implicating RGS9-2 as a candidate gene in schizophrenia.
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PMID:Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. 1731 83