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)

We investigated the mechanisms by which a serum activity, neither complement nor immunoglobulin, mediates killing of pneumococci by polymorphonuclear leukocytes (PMN). Electron microscopy revealed type 25 pneumococci to be within PMN when incubated in normal serum, in serum absorbed twice at 0 degrees C with type 25 pneumococci, or in absorbed plus heat-inactivated serum. Uptake of radiolabeled bacteria, and activation of oxygen consumption and of the hexose monophosphate shunt by PMN with pneumococci, were similar in normal serum, absorbed serum, or the combination of absorbed and heat-activated serum. Reduction of nitroblue tetrazolium (NBT) and of cytochrome c by PMN in the presence of type 25 pneumococci and absorbed serum, with or without heat-inactivated serum were one-third and one-half, respectively, of those in normal serum. Likewise, protein iodination was one-half that in normal serum. Reduction of cytochrome c by cytochalasin B-treated PMN was the same in normal, absorbed, or absorbed plus heat-inactivated serum. Furthermore, release of beta-glucuronidase from PMN after ingestion of pneumococci in 10% normal, absorbed, or absorbed plus heat-inactivated serum was identical. These data indicate that the "third" serum activity is not necessary for attachment of pneumococci to or ingestion by PMN, nor is it necessary for stimulation of the plasma membrane oxidase. Rather, it functions somehow in intracellular killing.
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PMID:Opsonization of pneumococci. II. Metabolic effects of a "third" human serum activity that mediates intracellular killing. 727 78

This study on human neutrophils was conducted to measure the kinetics of degranulation of the different cytoplasmic granules into phagocytic vacuoles, and to relate the timing of these events to the burst of respiration that accompanies phagocytosis by these cells. Purified neutrophils were incubated with latex particles opsonized with human immunoglobulin (Ig)G, and phagocytosis was stopped at timed intervals. The cells were examined by electron microscopy to document the sequence of degranulation of the cytoplasmic granules. The azurophil granules and lyosomes were identified by histochemical staining for peroxidase and acid phosphatase, respectively. Phagocytic vacuoles were separated from cell homogenates by floatation on sucrose gradients and assayed for contained lactoferrin, myeloperoxidase, and acid hydrolases. The conclusions drawn from the biochemical and morphological studies were in agreement and indicated: particle uptake and vacuole closure can be completed within 20 s; both the specific and azurophil granules fuse with the phagocytic vacuole much earlier than is generally appreciated, with half-saturation times of 39 s (99% confidence limits, 15-72); oxygen consumption has kinetics similar to those of the fusion of these granules with the phagosome; degranulation of the acid hydrolases beta-glucuronidase, N-acetyl-beta-glucosaminidase (biochemical assays), and acid phosphatase (biochemical assay and electron microscopic cytochemistry) have kinetics of degranulation that are similar to each other but totally different from and much slower than that of myeloperoxidase with half-saturation times of between 354 and 682 s (99% confidence limits, 246-883). This suggests that the acid hydrolases are not co-located with myeloperoxidase in the azurophil granule but are contained in distinct lysosomes, or "tertiary granules".
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PMID:Kinetics of fusion of the cytoplasmic granules with phagocytic vacuoles in human polymorphonuclear leukocytes. Biochemical and morphological studies. 736 74

The lysosomal enzymes, acid-phosphatase and beta-glucuronidase, were released from rat liver lysosome when exposed to 400 nm irradiation in the presence of haematoporphyrin, and the release was prevented by adding vitamin E, diazabicyclo-octane, bovine serum albumin, superoxide dismutase or D-mannitol to the reaction mixture. Monochromatic irradiation with wavelengths from 380 to 410 nm caused no significant differences in the release of lysosomal enzymes, but 420 nm irradiation caused three-fifths of that of 400 nm irradiation. The malondialdehyde level in rat liver homogenate increased after 400 nm irradiation in the presence of haematoporphyrin. Reduction of nitroblue-tetrazolium was not observed when haematoporphyrin was excited by 400 nm; it was considered that superoxide anion radical (O2--) was not primarily generated. The following mechanism was assumed: that porphyrin which had been excited by 400 nm, converted ground-state molecular oxygen (3O2) to excited singlet oxygen (1O2), which formed lipid peroxides in lysosomal membrane resulting in destruction of the membrane; skin changes would occur from these released lysosomal enzymes.
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PMID:Lysosome destruction and lipoperoxide formation due to active oxygen generated from haematoporphyrin and UV irradiation. 737 79

The actions of the novel metabolically stable and selective prostaglandin D2 receptor agonist ZK 118.182 ((5Z,13E)-(9R,11R,15S)-9-chloro-15-cyclohexyl-15- hydroxy-16,17,18,19,20-pentanor-3-oxa-5,13-prostadienoic acid) were studied in human platelets and polymorphonuclear neutrophils in vitro and compared to the naturally occurring agonist prostaglandin D2. ZK 118.182 inhibited collagen and ADP induced platelet aggregation more potently than prostaglandin D2 (IC50: 15 nM versus 60 nM) but was less effective than the stable prostacyclin mimetic iloprost (IC50: 3 nM). The same rank order of potencies was observed for the inhibition of collagen-induced platelet ATP secretion. A dose-dependent activation of adenylate cyclase could be demonstrated by ZK 118.182 which was comparable to that of prostaglandin D2 with respect to the concentration needed for half maximal stimulation (ED50) maximal cAMP level achievable. ZK 118.182 also dose dependently reduced the formyl-methionyl-leucyl-phenylalanine (FMLP) or platelet-activating factor (PAF) induced activation of polymorphonuclear neutrophils. Both, the oxygen burst resulting in the generation of superoxide anions and the degranulation of polymorphonuclear neutrophils accompanied by release of the lysosomal enzyme beta-glucuronidase, were significantly and dose dependently inhibited. ZK 118.182 was more potent than prostaglandin D2 in inhibiting polymorphonuclear neutrophil activation in all tests performed. In summary, ZK 118.182 is a prostaglandin D2 mimetic exerting potent inhibitory effects on human platelets and polymorphonuclear neutrophils.
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PMID:Inhibition of human platelets and polymorphonuclear neutrophils by the potent and metabolically stable prostaglandin D2 analog ZK 118.182. 752 76

The secretion of the Panton-Valentine leukocidin (Luk-PV) but not of another leukocidin (Luk-R) from Staphylococcus aureus strains is correlated with severe pyodermic infections (dermonecrosis). The effects of both Luk-PV and Luk-R in amounts of 0-5000 ng on inflammatory mediator release from human leukocytes were studied. Luk-PV but not Luk-R induced a pronounced release of the vasodilator histamine from human basophilic granulocytes (up to 55% +/- 7%) and of enzymes (beta-glucuronidase, up to 45% +/- 10%; lysozyme, up to 35% +/- 7%), chemotactic components leukotriene B4 (42 +/- 8 ng/10(7) cells) and interleukin-8 (up to 33 +/- 5 ng/10(7) cells), and oxygen metabolites from human neutrophilic granulocytes. The results indicate that granulocytes play a central role in dermonecrosis; these in vitro data account for the histologic picture of Luk-PV infections, characterized by local vasodilation, infiltration of granulocytes, and a central necrotic area.
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PMID:Effects of Staphylococcus aureus leukocidins on inflammatory mediator release from human granulocytes. 753 98

Chemical alteration of the glucocorticoid, methylprednisolone, has led to the introduction of a new class of compounds called the 21-aminosteroids (21-ASs). The purpose of this study was to investigate the effect of the 21-AS, U74389G, on silica-induced acute lung injury. Male Fischer 344 rats were treated intraperitoneally with saline or U74389G in a total dose of 15 mg/kg divided into three injections of 5 mg/kg separated by 4 h. Following the first treatment, animals from the two groups were intratracheally instilled with silica (10 mg/100 g body wt in 0.5 ml of saline) or saline vehicle (0.5 ml). Twenty-four hours after the instillations, bronchoalveolar lavage (BAL) was performed. In the animals not receiving U74389G, marked increases in total protein, beta-glucuronidase, and lactate dehydrogenase (LDH) activities and number of neutrophils (PMNs) were demonstrated in the BAL fluid of the silica-treated animals compared to their controls. Silica also caused dramatic increases in the luminol-dependent chemiluminescence (CL) of lung tissue and BAL cells. The CL reaction was decreased by superoxide dismutase (SOD) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide (NO) synthase inhibitor. In animals treated with U74389G, there was attenuation of the silica-induced increases in biochemical, cellular, and chemiluminescent indices of damage. This study demonstrates that U74389G significantly reduces acute lung injury caused by the intratracheal instillation of silica, and this drug may be of potential value for treatment of lung diseases in which damage caused by reactive oxygen species has been implicated.
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PMID:Attenuation of acute inflammatory effects of silica in rat lung by 21-aminosteroid, U74389G. 770 90

The nature of mutagenic burden due to occupational exposure to tobacco flakes and dust was determined among 20 female tobacco processors (TP) and 20 matched controls (C) by testing urinary mutagenicity in the Ames assay. In addition, urinary cotinine was estimated as a marker of tobacco absorption. Workers and controls were sub-divided into those with no tobacco habit (NH) and those habituated to the use of masheri (a pyrolysed form of tobacco) as a dentifrice (MH). Cotinine was not detected in samples from C-NH while the mean urinary cotinine levels in TP-NH and TP-MH were significantly higher than that in C-MH (3.46 +/- 0.95 and 3.57 +/- 0.46 versus 1.80 +/- 0.58 mM/M creatinine; P < 0.02). The majority of the urine samples from C-NH were non-mutagenic in the presence or absence of rat liver S9 while those from C-H were mutagenic to TA98 and TA102 strains upon metabolic activation. On the other hand, direct mutagenicity to TA98, TA100 and TA102 strains respectively was noted in 6/10, 5/10 and 8/10 samples from TP-NH and 7/10, 4/10 and 3/10 samples from TP-M. Generally, beta-glucuronidase treatment reduced or abolished the mutagenic potential of workers' urine samples indicating that glucuronide conjugates may have partially contributed to direct mutagenicity. Experiments using scavengers of reactive oxygen species revealed that direct mutagenicity in TA102 strain was mediated mainly via hydroxyl radicals. The results clearly demonstrate that tobacco processors are exposed to a wide spectrum of mutagens that cause frame-shift, base pair substitution and oxidative damage.
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PMID:Occupational exposure to unburnt bidi tobacco elevates mutagenic burden among tobacco processors. 776 70

The scavenging by procyanidines (polyphenol oligomers from Vitis vinifera seeds, CAS 85594-37-2) of reactive oxygen species (ROS) involved in the onset (HO degrees) and the maintenance of microvascular injury (lipid radicals R degrees, RO degrees, ROO degrees) has been studied in phosphatidylcholine liposomes (PCL), using two different models of free radical generation: a) iron-promoted and b) ultrasound-induced lipid peroxidation. In a) lipid peroxidation was assessed by determination of thiobarbituric acid-reactive substances (TBARS); in b) by determination of conjugated dienes, formation of breakdown carbonyl products (as 2,4-dinitrophenylhydrazones) and loss of native phosphatidylcholine. In the iron-promoted (Fenton-driven) model, procyanidines had a remarkable, dose-dependent antilipoperoxidant activity (IC50 = 2.5 mumol/l), more than one order of magnitude greater than that of the monomeric unit catechin (IC50 = 50 mumol/l), activity which is due, at least in part, to their metal-chelating properties. In the more specific model b), which discriminates between the initiator (hydroxyl radical from water sonolysis) and the propagator species of lipid peroxidation (the peroxyl radical, from autooxidation of C-centered radicals), procyanidines are highly effective in preventing conjugated diene formation in both the induction (IC50 = 0.1 mumol/l) and propagation (IC50 = 0.05 mumol/l) phases (the scavenging effect of alpha-tocopherol was weaker, with IC50 of 1.5 and 1.25 mumol/l). In addition, procyanidines at 0.5 mumol/l markedly delayed the onset of the breakdown phase (48 h), totally inhibiting during this time the formation of degradation products (the lag-time induced by alpha-tocopherol was only of 24 h at 10 mumol/l concentration). The HO degrees entrapping capacity of these compounds was further confirmed by UV studies and by electron spin resonance (ESR) spectroscopy, using DMPO as spin trapper: procyanidines markedly reduced, in a dose-dependent fashion, the signal intensity of the DMPO-OH radical spin adduct (100% inhibition at 40 mumol/l). The results of the second part of this study show that procyanidines, in addition to free radical scavenging action, strongly and non-competitively, inhibit xanthine oxidase activity, the enzyme which triggers the oxy radical cascade (IC50 = 2.4 mumol/l). In addition procyanidines non-competitively inhibit the activities of the proteolytic enzymes collagenase (IC50 = 38 mumol/l) and elastase (IC50 = 4.24 mumol/l) and of the glycosidases hyaluronidase and beta-glucuronidase (IC50 = 80 mumol/l and 1.1 mumol/l), involved in the turnover of the main structural components of the extravascular matrix collagen, elastin and hyaluronic acid.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Free radicals scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. 802 28

Superoxide dismutases (SODs) play a key role in the cellular defense against reactive oxygen species. To study the transcriptional regulation at the cellular level, the promoter of the Nicotiana plumbaginifolia cytosolic gene encoding Cu/ZnSOD (SODCc) was fused to the beta-glucuronidase (GUS) reporter gene (gusA) and analyzed in transgenic tobacco plants. The promoter was highly active in vascular bundles of leaves and stems, where it is confined to phloem cells. In flowers, GUS activity was detected in ovules and pollen grains, in pigmented tissues of petals, and in vascular tissue of ovaries and anthers. In response to treatment with the superoxide-generating herbicide paraquat, very strong GUS staining was observed in photosynthetically active cells of leaves and in some epidermal root cells of seedlings. The expression of the SODCc-gusA was also induced in seedlings after heat shock and chilling and after treatment with sulfhydryl antioxidants such as reduced glutathione and cysteine. It is postulated that SODCc expression is directly linked to a cell-specific production of excess superoxide radicals in the cytosol.
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PMID:Developmental and environmental regulation of the Nicotiana plumbaginifolia cytosolic Cu/Zn-superoxide dismutase promoter in transgenic tobacco. 816 60

Superoxide dismutases (SODs; superoxide: superoxide oxidoreductase, EC 1.15.1.1) play a key role in protection against oxygen radicals, and SOD gene expression is highly induced during environmental stress. To determine the conditions of SOD induction, the promoter of the cytosolic copper/zinc SOD (Cu/ZnSODcyt) gene was isolated in Nicotiana plumbaginifolia and fused to the beta-glucuronidase reporter gene. Oxidative stress is likely to alter the cellular redox in favor of the oxidized status. Surprisingly, the expression of the Cu/ZnSODcyt gene is induced by sulfhydryl antioxidants such as reduced glutathione, cysteine, and dithiothreitol, whereas the oxidized forms of glutathione and cysteine have no effect. It is therefore possible that reduced glutathione directly acts as an antioxidant and simultaneously activates the Cu/ZnSODcyt gene during oxidative stress.
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PMID:Redox-activated expression of the cytosolic copper/zinc superoxide dismutase gene in Nicotiana. 846 30


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