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 susceptibility of a number of human neutrophil granule enzymes to oxidative inactivation was investigated. Addition of H2O2 to the cell-free medium from stimulated neutrophils resulted in inactivation of all enzymes tested. This was inhibited by azide and methionine, indicating that inactivation was due to myeloperoxidase-derived oxidants. Lysozyme was more than 50% inactivated by one addition of 100 nmol of H2O2/ml, whereas myeloperoxidase, beta-glucuronidase, gelatinase and collagenase were almost completely inactivated by three additions. Cathepsin G was slightly less susceptible, whereas elastase was extremely resistant to oxidative attack. Myeloperoxidase-dependent enzyme inactivation may be a means whereby the neutrophil can terminate the activity of its granule enzymes and control the release of degradative enzymes into the tissues.
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PMID:Myeloperoxidase-dependent oxidative inactivation of neutrophil neutral proteinases and microbicidal enzymes. 282 16

Within 1 min of stimulation of human neutrophils by the chemotactic peptide (N-formyl-L-methionyl-L-leucyl-L-phenylalanine) plus cytochalasin B, myeloperoxidase (together with other granule enzymes) was secreted and detected extracellularly. In contrast with the other granule constituents assayed (vitamin B12-binding protein and beta-glucuronidase), the activity of released myeloperoxidase rapidly decreased, so that, by 10 min after stimulation, only about 5% of the total cellular activity was detected. This inactivation was shown to be dependent on oxidant generation during the respiratory burst, since inactivation was not observed (a) after stimulation of anaerobic suspensions or (b) after release from neutrophils from a patient with chronic granulomatous disease; purified myeloperoxidase was rapidly inactivated after incubation with H2O2, presumably owing to the formation of an inactive enzyme-H2O2 complex. These results show that experiments designed to assess the role of myeloperoxidase in neutrophil functions which utilize assays based on peroxidase activity will grossly underestimate this enzyme if oxidant generation during the respiratory burst has also been activated.
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PMID:Oxidative inactivation of myeloperoxidase released from human neutrophils. 282 34

Sphingoid long-chain bases (sphinganine and sphingosine) have recently been shown to inhibit protein kinase C both in vitro [Y. Hannun et al. (1986) J. Biol. Chem. 261, 12604-12609] and in intact human neutrophils, in which they block activation of the superoxide-generating respiratory burst [E. Wilson et al. (1986) J. Biol. Chem. 261, 12616-12623]. In the present study we have used sphingosine to investigate the pathways for agonist-induced secretion of neutrophil granule contents. Induction of secretion of the specific granule component lactoferrin by a variety of agonists [phorbol 12-myristate-13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), and calcium ionophore A23187] was completely inhibited by sphingosine with an ED50 of 6 to 10 microM. PMA-induced secretion of lysozyme (present in both the azurophilic and specific granules) was completely blocked with an ED50 of 10 microM, whereas fMLP-induced secretion was only about 50% inhibited. Secretion of the azurophilic granule proteins beta-glucuronidase and myeloperoxidase was activated by fMLP and A23187, but not by PMA, and was not affected by sphingosine. The use of A23187 in the presence of sphingosine allowed differentiation between calcium activation of protein kinase C-dependent versus-independent pathways. The effect of sphingosine was not mediated by neutralizing intracellular acidic compartments, since treatment of neutrophils with inhibitory concentrations of sphingosine did not significantly alter the uptake of labeled methylamine. We conclude that at least two mechanisms participate in the regulation of specific and azurophilic granule secretion, respectively: a protein kinase C-dependent pathway and a calcium-dependent pathway which does not involve protein kinase C.
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PMID:Protein kinase C inhibition by sphingoid long-chain bases: effects on secretion in human neutrophils. 282 97

The effects of several antioxidants on the three major functions of human neutrophils--oxidative burst, secretion and leukotriene formation--were investigated with special emphasis on the lipophilicity. The most striking differences were obtained when ascorbate and the lipophilic ester ascorbyl palmitate were compared. As expected, the luminol- and lucigenin-dependent chemiluminescence was inhibited by all antioxidants to a different degree. Ascorbyl palmitate was able to block the biphasic luminol-dependent response completely with IC50 values of 10 and 25 microM for the first and second phase, respectively. In contrast, ascorbate only blocked efficiently the first phase of the response. The secretion of elastase was inhibited by ascorbyl palmitate dose-dependently with an IC50 value of around 200 microM, whereas ascorbate was completely inactive. Electron microscopy supported the assumption that inhibition was due to a block in degranulation and not to enzyme inactivation. This was further supported by a parallel, although somewhat lower, inhibition of other secretory enzymes like myeloperoxidase, beta-glucuronidase or lysozyme. Cells treated with the Ca2+-ionophore A23187 responded by LTB4-synthesis which was also inhibited by ascorbyl palmitate. A very efficient inhibition was observed in cell homogenates with an IC50 value of 1.5 microM. No inhibition by ascorbate was detected in both systems. Concomitant with the inhibition of 5-lipoxygenase the activity of 15-lipoxygenase increased. We conclude that cellular reductants may control neutrophil functions and that the inhibition by ascorbyl palmitate of the three processes relevant for inflammatory responses could be of therapeutic importance.
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PMID:The suppression of granulocyte functions by lipophilic antioxidants. 283 72

Neutrophil level in blood (1 l) and those of certain enzymes in neutrophils were measured in 36 patients with stomach tumors and 40 healthy controls. The range of the enzymes included myeloperoxidase (MPO), beta-glucuronidase (GR), N-acetyl-beta-D-glucosaminidase (NAG), acid phosphatase (AcP), alkaline phosphatase (AlP), lactate dehydrogenase (LD) and dehydrogenase-glucoso-6-phosphoric acid (DG-6-P). Glycogen and lipids were also assayed. The MPO and AcP levels of neutrophils in cancer patients were found to be significantly higher than in healthy controls, whereas the levels of the other enzymes were not. The glycogen and lipid concentrations in neutrophils in cancer patients were significantly lower than in healthy controls.
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PMID:[Histochemical characteristics of neutrophils of the peripheral blood in patients with cancer of the stomach]. 283 37

The effect of the antimalarial drug mefloquine on human neutrophil degranulation, chemiluminescence, superoxide production and viability was examined in vitro. Mefloquine was found to significantly stimulate the release of lysozyme, beta-glucuronidase and myeloperoxide at a concentration of 10 micrograms/ml (2.5 X 10(-5) M) without loss of cell viability. At 40 micrograms/ml mefloquine (1 X 10(-4) M) cell viability was significantly decreased. Mefloquine at 10 micrograms/ml also significantly increased the release of lysozyme and beta-glucuronidase but not myeloperoxidase when neutrophils were stimulated with opsonized zymosan. At a lower zymosan concentration myeloperoxidase release was also increased. Enzyme activity was not directly stimulated by mefloquine. Mefloquine at 10 micrograms/ml significantly increased luminol-dependent chemiluminescence but significantly inhibited lucigenin-dependent chemiluminescence when neutrophils were stimulated with opsonized zymosan. Under these conditions superoxide release, measured by cytochrome c reduction, was inhibited to a lesser degree. These results are discussed with reference to our previous report that mefloquine inhibits the neutrophil iodination reaction [Immunology 58: 125-130, 1986] and the use of mefloquine as an anti-inflammatory drug.
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PMID:Stimulation of human neutrophil degranulation by mefloquine. 284 64

Because it has recently been hypothesized that human milk is antiinflammatory, the effects of aqueous human colostrum on human polymorphonuclear leukocyte (PMN) respiratory burst activity and selected enzymatic activities was examined. Aqueous colostrum was found to spontaneously reduce ferricytochrome C in a concentration-dependent manner, prohibiting use of the standard assay to measure superoxide production. It also caused a significant concentration-dependent prolongation of the lagtime from stimulation of PMN with phorbol myristate acetate to the appearance of hydrogen peroxide. Substitution of an enzymatic peroxide-generating system for PMN did not alter the effect of colostrum. Colostrum also suppressed myeloperoxidase activity and lysozyme activity, but not beta-glucuronidase activity in PMN lysates. Inclusion of colostrum in an in vitro assay of PMN-mediated cell detachment significantly suppressed this PMN-mediated effect. These data demonstrate that aqueous human colostrum significantly interferes with PMN oxygen metabolic and enzymatic activities that are important in the mediation of acute inflammation.
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PMID:Antioxidant properties of human colostrum. 284 22

The effects of nafazatrom on leukocyte function in vitro and in vivo were related to its ability to salvage ischemic myocardium in an occlusion-reperfusion model of myocardial injury in the anesthetized dog. Nafazatrom (0.4-75 microM) produced dose-related inhibition in vitro of neutrophil aggregation, superoxide anion generation, arachidonic acid metabolism, and, to a lesser extent, the release of beta-glucuronidase. In contrast, nafazatrom (0.4-37.5 microM) did not substantially influence platelet aggregation or the platelet metabolism of arachidonic acid. In vivo nafazatrom (10 mg/kg, po) reduced infarct size from 58 +/- 3% of the risk area (mean +/- SEM, n = 9) in control dogs to 23 +/- 2% of the risk area (n = 9, P less than 0.01). Nafazatrom also reduced the incidence of accompanying arrhythmias. Nafazatrom-induced myocardial salvage was not associated with any hemodynamic changes; moreover, it was independent of platelets, since thrombocytopenia did not prevent nafazatrom from exerting a protective effect. Measurements of the neutrophil-specific myeloperoxidase enzyme in ischemic myocardium indicate that the smaller infarct size in dogs treated with nafazatrom is accompanied by diminished leukocyte infiltration. Thus, the ability of nafazatrom to inhibit neutrophil function in vitro and cell infiltration in vivo may underly its myocardial-protective effects.
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PMID:Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function. 298 18

Coordinated observation of various factors in the inflammatory system and their relations shows that the levels of proamidase in granuloma pouch fluid in carrageenin-induced inflammation increase during the healing process whereas the proamidase shows (1) remarkably low values in rats injected with high doses of carrageenin, (2) low values in the earlier stages of inflammation with tissue damage (high values of fluid lipid peroxide and lactate dehydrogenase) and with phagocytosis (high values of fluid peroxidase and beta-glucuronidase), and (3) high values in the later stages where wound healing is progressing (high values of protein in plasma, fluid and granuloma pouch tissue and low values of fluid volume, fluid peroxidase, beta-glucuronidase and pouch tissue weight). In short, proamidase shows low values in the stage of tissue damage and constantly increasing values during the process of healing. Thus the measurement of proamidase, which reflects the degree of wound healing, provides an important parameter for a broad, coordinated observation of the inflammatory process, and may enable the management of inflammation.
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PMID:Management of inflammation: proamidase as a parameter for a better understanding of inflammatory processes. 298

Chemotactic factors can cause polymorphonuclear leukocytes to release the contents of azurophilic granules, including the enzymes beta-glucuronidase and myeloperoxidase. In the presence of aqueous humor from the anterior chamber of the rabbit eye, the supernatant from stimulated leukocytes contains beta-glucuronidase, but myeloperoxidase is not detectable. Studies with aqueous humor and partially purified human myeloperoxidase suggest that this phenomenon is not due to a failure of enzyme release. The factor responsible for the inability to detect MPO in the assay system is heat-labile, dialyzable, and reversed by ascorbate oxidase. Comparable assay inhibition is produced by ascorbic acid at a concentration present in either human or rabbit aqueous humor. The ability of aqueous humor to protect against myeloperoxidase-induced oxidation may contribute to several diverse phenomena, including the susceptibility of the eye to Candida infection and a prolonged half-life for several inflammatory mediators in the anterior chamber.
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PMID:Ascorbate in aqueous humor protects against myeloperoxidase-induced oxidation. 299 83


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