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)

Biochemical mechanisms underlying acrylamide induced neurotoxicity were examined using an in vitro model consisting of sagittal slices of rat brain. Incubation of brain slices under oxygen in artificial cerebrospinal fluid containing acrylamide produced a dose and time dependent inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Lysosomal enzymes, acid phosphatase, N-acetyl glucosaminidase and beta-glucuronidase decreased in a similar manner, while no changes were observed in the activity of Na+K+ATPase, cytochrome c oxidase and lactate dehydrogenase. Incubation of slices with two structurally related compounds, acetamide (a non-neurotoxic amide) and methylene bis-acrylamide (a weak neurotoxin), indicated that acrylamide selectively inhibited GAPDH, enolase and N-acetyl glucosaminidase at low concentration; similar doses of acetamide and methylene bis-acrylamide did not have the same effect on brain slices. Incubation with acrylamide depleted glutathione levels in slices, and the addition of glutathione to the incubation medium prevented acrylamide induced inhibition of GAPDH and lysosomal enzymes. Time dependent inhibition of lysosomal enzymes was also observed in vivo, in the brain and sciatic nerve of rats following a single dose of acrylamide. These results demonstrate that both in vitro and in vivo, lysosomal enzymes are also inhibited following acrylamide exposure. The rat brain slice model exhibits both selectivity and sensitivity towards neurotoxicants and hence, may prove to be an useful in vitro model for the mechanistic evaluation of neurotoxicity.
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PMID:The use of rat brain slices as an in vitro model for mechanistic evaluation of neurotoxicity-studies with acrylamide. 195 83

Zinc is a physiological constituent of many human enzymes and also involved in an optimal immune response. Zinc deficiency as well as excessive zinc supplementation lead to disturbed functions of immune cells. In this study with isolated human polymorphonuclear leukocytes the toxic oxygen species generated during the oxidative metabolism were enhanced in presence of zinc ions. However, when the generation of superoxide anion was measured alone it was decreased by zinc. The phagocytic capacity was diminished in presence of zinc ions, too. The release of lysosomal enzymes was not influenced (lysozyme) or weakly inhibited (beta-glucuronidase). Our results may indicate an impairment of the microbicidal capacity due to the diminished phagocytosis, but a promotion of inflammatory reactions due to an increase of toxic oxygen species in the presence of zinc ions.
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PMID:Alterations of the oxidative metabolism and other microbicidal activities of human polymorphonuclear leukocytes by zinc. 196 62

lpsZ+ is an allele that allows exo (exopolysaccharide-deficient) mutants of Rhizobium meliloti to invade nodules by modifying rhizobial lipopolysaccharide. We have cloned and sequenced the lpsZ gene. The predicted LpsZ protein has a molecular weight of 48,589 and is probably localized in the cytoplasm. A beta-glucuronidase fusion in the lpsZ gene indicates that lpsZ is not regulated by oxygen or nitrogen.
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PMID:lpsZ, a lipopolysaccharide gene involved in symbiosis of Rhizobium meliloti. 202 21

This study determined the effect of blood leucocyte depletion on the early inflammatory response of the lung to alpha-quartz. F344/N rats were instilled intratracheally with either physiological saline or 2 or 5 mg of alpha-quartz suspended in saline. One day prior to the instillation, half of the rats received an ip injection of rabbit antiserum that had been raised against rat neutrophils. The other half of the rats received an ip injection of normal rabbit serum. One day after the instillation of saline or quartz, the animals were euthanized and observed for changes in blood cell numbers, lung histopathology, and bronchoalveolar lavage fluid (BALF) content of indicators of an inflammatory response and cytotoxicity. The rabbit antiserum depleted the blood of most white blood cells of all types. BALF fluid from saline-instilled animals did not differ between the white blood cell-depleted and the nondepleted animals except for a 20% reduction in numbers of alveolar macrophages in the depleted animals. BALF fluid from the nondepleted, quartz-instilled animals had a dose-dependent increase in content of neutrophils and protein (indicator of an increase in the permeability of the alveolar/capillary barrier) as well as an increase in lactate dehydrogenase and glutathione reductase (cytoplasmic enzymes whose presence extracellularly indicates cytotoxicity), alkaline phosphatase (indicator of type II cell secretory activity), beta-glucuronidase, and acid proteinase (lysosomal enzymes) activities. The higher dose of quartz also elicited an increase in LTB4 and PGE2 content of BALF. GSH content of BALF was decreased by the quartz exposure. The depletion of blood white blood cells prevented the influx of neutrophils into the alveoli of the quartz-exposed rats and decreased the BALF markers of capillary permeability and cytotoxicity (protein content and extracellular cytoplasmic enzymes). The absence of neutrophils in the alveoli had no effect on the lysosomal content of BALF, indicating that the neutrophils were not the source of these enzymes in nondepleted rats exposed to alpha-quartz. The quartz-induced elevation of LTB4 in BALF was not observed in depleted rats, suggesting that neutrophils may be the source of the increase in this leukotriene in the BALF. Both the GSH content and the alkaline phosphatase activity in BALF were enhanced in the absence of alveolar neutrophils. The enhancement of GSH in BALF is consistent with the neutrophils being the source of reactive oxygen species that deplete GSH. The increased alkaline phosphatase activity in the BALF of both the depleted and nondepleted animals is consistent with the type II cell hypertrophy that was induced by quartz instillation and was neutrophil independent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of blood leucocyte depletion on the inflammatory response of the lung to quartz. 203 43

This study was designed to investigate effects of cellular injury mediated by oxygen-derived free radicals on the intestine, heart, liver, kidney and lung tissues during superior mesenteric artery occlusion shock in rats. The animals were divided into four groups: control (Group 1, n = 6), one hour occlusion (Group 2, n = 8), one hour after releasing the clamp (Group 3, n = 8), and two hours after releasing the clamp (Group 4, n = 8). Compared to control values, the contents of malondialdehyde (MDA) in each tissue in Group 2 had 110 significant changes (P greater than 0.05); in Group 3, MDA in the intestine and heart tissues significantly elevated by 62% (P less than 0.05) and 56% (P less than 0.05); in Group 4, MDA in the intestine, heart, liver, and lung tissues increased by 121% (P less than 0.01), 65% (P less than 0.05), 32% (P less than 0.05), and 31% (P less than 0.05), respectively. Plasma lactic acid, beta-glucuronidase and acid phosphatase increased significantly (P less than 0.01). The results showed that oxygen-derived free radical could cause lipid peroxidation damage not only in the intestine tissue, but also in the heart, liver, and lung tissues, suggesting that oxygen-derived free radicals might play an important role in cellular injury during superior mesenteric artery occlusion shock.
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PMID:Role of oxygen-derived free radicals in superior mesenteric artery occlusion shock in rats. 211 38

The action of PGE1, PGE2, PGI2 and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca2+ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, beta-glucuronidase release (IC50 3-5 mumol/l) and Ca2+ influx while PGI2 and iloprost were ineffective at concentrations up to 10 mumol/l. These inhibitory actions of PGE1 and PGE2 were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI2 and iloprost. None of the prostaglandins affected the initial intracellular Ca2+ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE1 and PGE2 but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187). These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE1 and PGE2 might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i.e. inflammatory reactions.
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PMID:Cytotoxic enzyme release and oxygen centered radical formation in human neutrophils are selectively inhibited by E-type prostaglandins but not by PGI2. 215 12

We studied the effects of exogenous, purified phospholipase C (PLC) on neutrophil oxidative metabolism, lysosomal enzyme release and aggregation. We found that PLC inhibited O2- and H2O2 generation and oxygen consumption, but did not alter glucose oxidation via the hexose monophosphate shunt. In contrast, we found a striking stimulation of aggregation and release of the lysosomal enzymes lysozyme and beta-glucuronidase. In experiments designed to further characterize the mechanism of the PLC effect on membrane activation we studied the effect of PLC on intracellular calcium concentration [Ca2+]i and found that PLC did not interfere with the fMLP-mediated rise in [Ca2+]i, suggesting that its inhibitory effect on the respiratory burst does not involve inhibition of early signal transduction events. In addition, we found that PLC alone results in mobilization of intracellular Ca2+ stores, consistent with its stimulatory effect on aggregation and lysosomal enzyme release.
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PMID:Inhibition of polymorphonuclear leukocyte oxidative metabolism by exogenous phospholipase C. 216 37

Studies in rats indicate that neutrophils (polymorphonuclear leukocytes (PMNs] are associated with areas of tissue damage after treatment with the hepatotoxicant, alpha-naphthylisothiocyanate (ANIT). Several synthetic and naturally occurring substances stimulate PMNs to release cytotoxic mediators, such as superoxide (O2-). The purpose of the present study was to test the hypothesis that ANIT stimulates the release of O2- from isolated rat PMNs. PMNs derived from rat peritoneum were treated with ANIT in vitro and tested for release of O2-. ANIT caused the release of O2- from PMNs in a concentration-dependent manner. Maximal O2- release (10 +/- 1 nmoles/30 minutes/2 x 10(6) cells) was achieved by an ANIT concentration of 110 microM. This ANIT-induced O2- release was significantly reduced or blocked completely by preincubation of PMNs for 10 minutes with 10 microM or 100 microM SKF 525A, respectively. The beta-isomer of ANIT, which does not cause cholestasis in vivo, did not stimulate O2- release. ANIT-stimulated O2- production decreased sharply after 5 minutes of incubation with ANIT and ceased entirely between 10 to 15 minutes. Shortly after this decrease in O2- production was an increase in the extracellular activity of lactate dehydrogenase. PMNs exposed to ANIT also failed to exclude trypan blue dye, either in the presence or in the absence of superoxide dismutase and catalase, suggesting a direct, oxygen radical-independent, cytotoxic effect of ANIT on PMNs. Release of the lysosomal enzyme, beta-glucuronidase, occurred within 5 minutes of incubation of isolated PMNs with ANIT (110 microM). These results indicate that exposure of rat PMNs to the hepatotoxicant, ANIT, causes the release of cytotoxic agents, whereas its less hepatotoxic beta-isomer does not.
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PMID:The cholestatic agent, alpha-naphthylisothiocyanate, stimulates superoxide release by rat neutrophils in vitro. 216 98

This study was designed to investigate the beneficial effect of administration of exogenous superoxide dismutase (SOD) on the inhibition of lipid peroxidation and cellular protection during superior mesenteric artery occlusion shock in rats. Wistar rats were anesthetized with sodium pentobarbital (30 mg/kg body weight), and the superior mesenteric artery occlusion shock model was induced by clamping the superior mesenteric artery for a 60-min period and then releasing the arterial clamp. The following parameters were determined: 1) average arterial blood pressure; 2) survival rate and mean survival time (MST); 3) activities of plasma lysosomal enzymes beta-glucuronidase (beta-G) and acid phosphatase (ACP); and 4) the contents of malondialdehyde (MDA) in visceral tissues. The SOD group received 15,000 U/kg body weight SOD intra-arterially 15 min before release of the clamp. The saline group received intra-arterially a corresponding volume of saline given to the SOD group. The superior mesenteric artery of rats in the control group was not clamped. In the saline group, the contents of MDA presented significant increases (P less than 0.05) in bowel and heart tissues at 1 hr after release of the clamp and showed more significant increases (P less than 0.01-0.05) in bowel, heart, liver, and lung tissues at 2 hr after release of the clamp, when compared with control values. However, the contents of MDA in bowel and heart tissues in the SOD group showed significant decreases (P less than 0.05) compared with values in the saline group and had insignificant changes (P greater than 0.05) compared with control values at 1 hr after release of the clamp. The contents of MDA in bowel, heart, and lung tissues in the SOD group were still lower than those in the saline group (P less than 0.05) at 2 hr after release of the clamp, although they were higher than those in the control group (P less than 0.05). The activities of plasma lysosomal enzymes in the SOD group were much lower than those in the saline group at 1 and 2 hr after release of the clamp. The mean survival time of shocked animals was prolonged when treated with SOD. These results suggested that administration of exogenous SOD may protect cells against lipid peroxidation injury mediated by oxygen-derived free radicals, depress the release of lysosomal enzymes, and prolong the mean survival time of shocked animals.
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PMID:Oxygen-derived free radicals induced cellular injury in superior mesenteric artery occlusion shock: protective effect of superoxide dismutase. 220 5

The production of delta-toxin is supposed to be responsible for various pathophysiological effects during infection with Staphylococcus aureus. We compared the effects of delta-toxin with the structurally related bee venom toxin melittin on granulocyte functions and inflammatory mediator release. Delta-toxin and melittin induced a rapid Ca2+ influx, as was shown by fluorescence detection. Furthermore, oxygen radical production, as determined by luminol-enhanced chemiluminescence, was triggered by delta-toxin (0.15 to 15 micrograms/ml), whereas melittin showed only marginal effects. Release of lysozyme and beta-glucuronidase was observed only at high concentrations of 15 micrograms of melittin and delta-toxin per ml. Preincubation (15 min) of neutrophils with both toxins resulted in the formation of 3H-platelet-activating factor (3H-PAF) from 3H-lyso-PAF. After 5 min of incubation, the exogenously added lyso-PAF was converted to PAF (delta-toxin, 80 +/- 2%; melittin, 27 +/- 12% of total radioactivity; n = 3, mean +/- standard error of the mean) and 1-O-alkyl-2-acyl-glycerophosphorylcholine (alkyl-acyl-GPC) (corresponding values, 20 +/- 3% and 51 +/- 14% of total radioactivity). The newly generated PAF was rapidly metabolized to lyso-PAF and alkyl-acyl-GPC during the subsequent incubation period of 60 min. In the absence of any toxin, no formation of PAF from lyso-PAF was observed. Further studies indicated that the metabolism of PAF into lyso-PAF and alkyl-acyl-GPC was inhibited in the presence of delta-toxin. Melittin had no significant effects on PAF metabolism. Neither delta-toxin nor melittin modulated the uptake of PAF and lyso-PAF significantly. Our data provide evidence that delta-toxin has an effect on the activity of neutrophil granulocytes with regard to its proinflammatory capacity.
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PMID:Effect of Staphylococcus aureus delta-toxin on human granulocyte functions and platelet-activating-factor metabolism. 234 Nov 70


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