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)

Neutrophil (PMN) contributions to the acute inflammatory process and host defense include generation of bioreactive oxygen metabolites and secretion of granule enzymes. We assessed equine PMN secretion using several PMN stimuli, singly and in combination with bacterial lipopolysaccharide (LPS). LPS avidly associated with equine PMN, as shown by strong PMN labeling with FITC-conjugated LPS. LPS alone (1 or 10 micrograms ml-1) was a weak stimulus for PMN superoxide anion (O2-) generation, but preincubation with LPS followed by phorbol ester (PMA, 10 ng ml-1) significantly augmented (P less than 0.01) secretion of O2- (19.38 nmol O2- per 2 x 10(6) PMN per 5 min) over the amount generated by PMA stimulation alone (13.75 nmol O2-). A qualitatively similar, but smaller O2(-)-generation response occurred when either opsonized zymosan or recombinant human C5a was used as the PMN stimulus. Arachidonic acid (ArA; 50-200 microM) was a potent stimulus, with secreted O2- levels similar to those from PMA-stimulated PMN. Preincubation of PMN with either the formyl peptide, fMLP, or platelet-activating factor before stimulation with ArA did not significantly increase O2- generation over levels obtained using ArA alone. Release of PMN granule enzymes was also quantitated. A small amount of lysozyme secretion resulted when PMN were exposed to LPS alone (8.20% of total cell content), and PMA stimulation caused marked release of PMN lysozyme (44.45%). Non-specific proteolytic activity in PMN supernatants, assessed by cleavage of a collagen-rich substrate, was minimal with LPS as a sole stimulus (5.08%). There was significant proteolytic activity (P less than 0.01) in supernatants from PMA-stimulated PMN (27.21%), and preincubation with LPS followed by PMA stimulation slightly enhanced (P less than 0.05) the release of PMN proteases (34.62%). The activities of beta-glucuronidase, acid phosphatase, and alkaline phosphatase were minimal in PMN supernatants when using LPS and PMA as stimuli. The activity of PMN granule enzymes was found to be sensitive to the presence of normal equine serum, and proteolytic activity was markedly reduced (80.13% reduction) in the presence of 10% pooled serum.
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PMID:Secretory activity of equine polymorphonuclear leukocytes: stimulus specificity and priming effects of bacterial lipopolysaccharide. 131 72

Arachidonic acid metabolism in resident rat alveolar macrophages and in those activated with complete Freund's adjuvant (CFA) was studied. Adult Sprague-Dawley rats were injected with 0.05 ml CFA, and macrophages were harvested 10 days later. Macrophages were labeled overnight with carbon 14-labeled arachidonic acid, washed, and then stimulated with calcium ionophore A23187 (IoA), phorbol myristate acetate (PMA), or zymosan for 30 minutes. Prostaglandins, thromboxane, and leukotrienes were extracted from the medium and analyzed by radioimmunoassay or radio high-pressure liquid chromatography. Cell lipids were analyzed by radio thin-layer chromatography. Medium and cell beta-glucuronidase activity and protein kinase C activity of the membrane fraction were also assayed. We found (1) lower leukotriene B4 (LTB4) production in stimulated resident macrophages when compared with resident macrophages after IoA stimulation--the suppressed LTB4 production was reversed by PMA; (2) unchanged or higher LTB4 production in activated macrophages when compared with resident macrophages after zymosan stimulation; (3) inhibition of zymosan-stimulated LTB4 production by staurosporine, a protein kinase C inhibitor, in both groups; and (4) lower diacylglycerol (DAG) production in activated macrophages when compared with resident macrophages after IoA stimulation, but not after zymosan stimulation. These results suggest that the reduced response of activated macrophages to IoA is due to decreased production of an endogenous protein kinase C activator. This hypothesis was further supported by the observation that protein kinase C activation in response to IoA was lower in activated macrophages than in resident macrophages. In contrast, zymosan stimulation resulted in higher protein kinase C activation in activated macrophages when compared with resident cells. We hypothesize that protein kinase activation is necessary for leukotriene production and that the preserved ability of zymosan to activate PKC via DAG accounts for the high leukotriene production in zymosan-activated macrophages. We also found that stimulated thromboxane production was higher in activated than resident cells, regardless of the stimulus, and that thromboxane production was not affected by staurosporine. Thus alterations of eicosanoid metabolism in immunologically activated macrophages depend on the stimulus used and the type of eicosanoid examined. Furthermore, leukotriene biosynthesis in rat alveolar macrophages may be regulated by protein kinase C.
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PMID:Production of leukotrienes and thromboxane by resident and activated rat alveolar macrophages: a possible role of protein kinase C. 132 31

Arachidonate metabolites appear to be involved in lung injury caused by cobra venom factor (CVF)-induced complement and polymorphonuclear leukocyte (PMN) activation. These studies were designed to assess the effects of a dietary-induced deficiency of arachidonic acid on CVF-induced lung injury. Rats raised on an essential fatty acid-deficient (EFAD) diet exhibited the expected changes in fatty acid composition including decreased plasma levels of arachidonic acid and increased levels of 5,8,11-eicosatrienoic acid. In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury, as evidenced by increased 125I-labeled bovine serum albumin accumulation in lung parenchyma and alveolar lavage fluid. The CVF-induced pulmonary artery pressor response and lung injury were reduced when blood perfusate or blood perfusate and excised lungs were obtained from rats raised on the EFAD diet. The pulmonary vascular constriction and lung injury were not attenuated when the blood perfusate was obtained from rats raised on the normal diet, irrespective of whether the excised lungs were obtained from rats raised on the normal or EFAD diet. PMNs obtained from rats raised on the EFAD diet demonstrated decreased superoxide production as well as impaired random migration and chemotaxis in vitro. In contrast, beta-glucuronidase release was quantitatively similar to PMNs from control rats. These data indicate that the EFAD diet-induced attenuation of CVF-induced pulmonary hypertension and acute lung injury is due to defective effector cells in blood rather than modified pulmonary target tissue.
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PMID:Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet. 280 79

We have studied the role of arachidonic acid (AA) metabolism in the release of lysosomal enzymes (beta-glucuronidase and lysozyme) from human polymorphonuclear leukocytes (PMNs). 5,8,11,14-Eicosatetraenoic acid (ETYA), which inhibits both the cyclo-oxygenase and the lipoxygenase pathways of AA metabolism, was found to cause a dose-dependent inhibition of lysosomal enzyme release from human PMNs induced by immunological (i.e., serum-treated zymosan: Zx) and nonimmunological stimuli (i.e., formyl methionine-containing peptide and the Ca2+ ionophore A23187). In contrast, the non-steroidal anti-inflammatory drugs (indomethacin, meclofenamic acid and aspirin), which only block the cyclo-oxygenase pathway of AA metabolism, had little effect on enzyme release from PMNs induced by the same stimuli. 5,8,11-Eicosatriynoic acid (ETI), a selective inhibitor of the lipoxygenase pathway of AA metabolism, caused a dose-dependent inhibition of lysosomal enzyme release elicited by Zx, f-met peptide, and A23187. p-Bromophenacyl bromide (BPB), which inhibits the phospholipase A2 (PLA2) activity in several tissues, was found to cause a dose-dependent inhibition of lysosomal enzyme release induced by the same immunological and non-immunological stimuli. The inhibitory effect of BPB on enzyme release was irreversible and extremely rapid. It appears that activation of PLA2 and the products of the AA metabolism, generated via a lipoxygenase pathway, play an essential role in the biochemical control of human PMNs activation and secretion.
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PMID:Possible role of arachidonic acid and of phospholipase A2 in the control of lysosomal enzyme release from human polymorphonuclear leukocytes. 664 91

Arachidonate (1-300 microM) mobilized Ca2+ ions from an intracellular store and stimulated the entry of Ca2+ ions from the extracellular fluid in undifferentiated HL-60 cells that had been loaded with Fura-2. The integrated response was biphasic in form: arachidonate liberated Ca2+ ions from the intracellular store first, resulting in a transient increase in cytosolic free Ca2+ concentration ([Ca2+]i). Ca2+ entry from the extracellular fluid was not evident for a further 1-2 min. At baseline, [Ca2+]i was 48.1 +/- 14.0 nM (SEM, n = 5). Upon addition of arachidonate (100 microM), [Ca2+]i rose to a transient peak level of 217 +/- 38.6 nM (SEM, n = 5) and a later plateau level of 427 +/- 118 nM (SEM, n = 5). Removal of added Ca2+ ions from the extracellular fluid in the presence of EGTA (1.0 mM) had no effect on the initial transient response but abolished the second phase of the response. In HL-60 cells that had been loaded with BAPTA/AM, the initial transient phase of the response was abolished but the elevation in [Ca2+]i due to Ca2+ entry from the extracellular fluid was unaffected. Undifferentiated HL-60 cells also responded to arachidonate (100 microM) with an increase in the release of the lysosomal enzyme beta-glucuronidase. Arachidonate-induced beta-glucuronidase release from BAPTA-loaded cells or in control cells exposed to Ca(2+)-free solutions was inhibited by about 50%. In BAPTA-loaded cells that were incubated with Ca(2+)-free solutions, arachidonate-induced beta-glucuronidase release was inhibited by about 90%. Leukotriene B4 failed to elevate [Ca2+]i in the concentration range 0.01-1 microM and failed to activate beta-glucuronidase release in concentrations up to 10 microM. Furthermore, the cyclo-oxygenase/lipoxygenase inhibitor ETYA (100 microM) was without effect on secretion. Consistent with this finding, we found that a large number of unsaturated fatty acids could reproduce the effect of arachidonate on [Ca2+]i and beta-glucuronidase release. Fatty acids belonging to the omega-3, omega-6 and omega-7 unsaturated fatty acid families were effective in elevating [Ca2+]i and stimulating beta-glucuronidase release. However, three unsaturated fatty acids, all belonging to the omega-9 fatty acid family, were ineffective.
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PMID:Arachidonate and other fatty acids mobilize Ca2+ ions and stimulate beta-glucuronidase release in a Ca(2+)-dependent fashion from undifferentiated HL-60 cells. 852 54

Eleven chalcone derivatives have been tested for their inhibitory effects on platelet aggregation in rabbit platelet suspension and the activation of mast cells and neutrophils. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the compounds and some also had a potent inhibitory effect on collagen-induced platelet aggregation and cyclooxygenase. Some hydroxychalcone derivatives showed strong inhibitory effects on the release of beta-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti-inflammatory effect of 2',5'-dihydroxychalcone was greater than that of trifluoperazine. 2'5'-Dihydroxy and 2',3,4,5'-tetrahydroxyl chalcones, even at low concentration (50 microM), tested in platelet-rich plasma from man almost completely inhibited secondary aggregation induced by adrenaline. These results suggest that the anti-platelet effects of the chalcones are mainly a result of inhibition of thromboxane formation.
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PMID:2',5'-Dihydroxychalcone as a potent chemical mediator and cyclooxygenase inhibitor. 917 90