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)

Eighteen synthetic xanthone derivatives were tested for their inhibitory effects on the activation of mast cells and neutrophils. 1,3- and 3,5-Dihydroxyxanthone showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. 1,6-Dihydroxyxanthone and 1,3,8-trihydroxyxanthone showed strong inhibitory effects on the release of beta-glucuronidase, and beta-glucuronidase and lysozyme, respectively, from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). 1,3- and 1,6-Dihydroxyxanthone, 1,3,7-trihydroxyxanthone, and 1,3,5,6-, 2,3,6,7-, and 3,4,5,6-tetrahydroxyxanthone showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP. 1,6- and 3,5-Dihydroxyxanthone showed remarkable inhibitory effects on hind-paw oedema induced by polymyxin B in normal as well as in adrenalectomized mice. These data indicated that the anti-inflammatory effect of these compounds is mediated through the suppression of chemical mediators released from mast cell and neutrophil degranulation.
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PMID:Synthesis and anti-inflammatory effects of xanthone derivatives. 879 82

Stereochemically constrained extended beta-antiparallel and folded beta-turn analogs of the chemotactic agent N-formyl-Met-Leu-Phe-OH were tested for their ability to induce the release of beta-glucuronidase from human and rabbit neutrophils. Selected biologically active peptides were further examined for their capacity to inhibit the binding of f-Met-Leu-[3H]Phe to whole human neutrophils at 4 degrees C. The results suggest that Dpg2 analogs with the extended backbone are significantly more potent in human peripheral blood neutrophils than the folded beta-turn analogs. Surprisingly, in rabbit peritoneal neutrophils, the extended Dpg2 analog appears to be marginally less active than the flexible parent peptide and the folded Ac6c2 analog. In human neutrophils, the secretagogue activity increases in the following order with alteration in the C-terminal functions: -CONH2 < -COOMe < -COOH << -COOBzl. However, this order of potency differs from that observed for the rabbit formyl peptide receptor (-COOH < -COOMe < -CONH2 << -COOBzl). In human neutrophils, the peptides' ability to compete for the receptor binding site of f-Met-Leu-[3H]Phe correlates well with their secretagogue potency. The results provide convincing evidence for the existence of subtle differences between human peripheral blood neutrophils and rabbit peritoneal neutrophils with regard to ligand-receptor interactions of constrained chemotactic peptides. What is new and novel in this report is that constrained peptides can distinguish between the rabbit and human chemotactic peptide receptors which have so far been believed to have similar response to secretagogue agents. The data emphasize that directly relating the secretagogue activity observed in rabbit neutrophils to that observed in human neutrophils may not be unequivocal.
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PMID:Subtle differences between human and rabbit neutrophil receptors shown by the secretagogue activity of constrained formyl peptides. 901 22

Neutrophils contain various antibacterial polypeptides and proteins in the granules. Defensins have been known as the major antimicrobial granular components. Recently, we have purified a novel cationic antibacterial polypeptide of 11 kDa (CAP11) from guinea pig neutrophil granules. In this study, we have examined the extracellular release and biological activity of CAP11, and compared with defensins. CAP11 was extracellularly released from neutrophils by N-formyl Met-Leu-Phe, phorbol 12-myristate 13-acetate, accompanied by the release of lysozyme, a specific and azurophil granule component, without release of beta-glucuronidase, an azurophil granule component, whereas defensins were released by phagocytosis, accompanied by the release of beta-glucuronidase, suggesting that the localization of CAP11 and defensins is different among neutrophil granules. Defensins increased neutrophil adhesion, and inhibited phagocytosis of opsonized zymosan particles and phagocytosis-associated superoxide anion generation. In contrast, CAP11 did not affect these neutrophil functions. Both CAP11 and defensins possessed the histamine-releasing activities for mast cells, but CAP11 was 10-fold less potent than defensins. CAP11 and defensins showed the antibacterial activities against both Escherichia coli and Staphylococcus aureus. However, the antibacterial activity of defensins was completely lost in the presence of physiological concentration of NaCl (0.15 M), although CAP11 retained the antibacterial activity even in the presence of NaCl. Furthermore, CAP11 exhibited the 10-fold more potent antiretroviral activity than defensins against Moloney murine leukemia viruses. Together these observations indicate that when released from neutrophils, CAP11 likely functions as an antimicrobial molecule in the extracellular milieu, whereas defensins may participate in the modulation of neutrophil function and mast cell histamine release.
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PMID:Comparative studies on the extracellular release and biological activity of guinea pig neutrophil cationic antibacterial polypeptide of 11 kDa (CAP11) and defensins. 908 Jun 67

The ubiquitin pathway targets proteins for degradation through the post-translational covalent attachment of the 76 amino acid protein ubiquitin to epsilon-amino lysyl groups on substrate proteins. Two instability determinants recognized by the ubiquitin pathway in Saccharomyces cerevisiae have been identified. One is described by the N-end rule and requires specific destabilizing residues at the substrate protein N-termini along with a proximal lysyl residue for ubiquitin conjugation. The second is a linear uncleavable N-terminal ubiquitin moiety. The ability of these two determinants to function in higher plants was investigated in tobacco protoplast transient transfection assays using DNA encoding variants of well characterized reporter enzymes as substrates: firefly luciferase that is localized to peroxisomes (pxLUC), a cytosolic version of LUC (cLUC), and Escherichia coli beta-glucuronidase (GUS). cLUC with phenylalanine encoded at its mature N-terminus was 10-fold less abundant than cLUC with methionine at its mature N-terminus. GUS with phenylalanine encoded at its mature N-terminus was 3-fold less abundant than GUS with methionine at its mature N-terminus. The presence of a uncleavable N-terminal ubiquitin fusion resulted in 50-fold lower protein accumulation of cLUC, but had no effect on GUS. Both instability determinants had a much larger effect on cLUC than on pxLUC, suggesting that these degradation signals are either unrecognized or poorly recognized in the peroxisomes.
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PMID:Engineering in vivo instability of firefly luciferase and Escherichia coli beta-glucuronidase in higher plants using recognition elements from the ubiquitin pathway. 961 5

The process of degranulation of mast cells and neutrophils contributes to inflammatory disorders. Activation of microglial cells and macrophages is believed to be involved in inflammatory, infectious and degenerative diseases of the CNS. Combining the potent inhibition of chemical mediators released by the degranulation of mast cells or neutrophils and from the activated microglial cells or macrophages, would lead to a promising anti-inflammatory agent for the treatment of peripheral and central inflammation. A series of chalcone derivatives have been reported to have potent anti-inflammatory activity. In an effort to continually develop potent anti-inflammatory agents, novel series of chalcones, 2'-hydroxy- and 2',5'-dihydroxychalcones were synthesized and their inhibitory effects on the activation of mast cells, neutrophils, microglial cells and macrophages were evaluated in-vitro. The chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with an appropriate aromatic aldehyde. The alkoxychalcones were prepared with appropriate hydroxychalcones and alkyl iodide and the dihydroxychalcones were prepared by hydrogenation of an appropriate chalcone with Pd/C. Almost all of the hydroxychalcones exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Of the hydroxychalcones, compound 1 was the most potent inhibitor of the release of beta-glucuronidase (IC50=1.6+/-0.2 microM) and lysozyme (IC50=1.4+/-0.2 microM) from rat neutrophils stimulated with fMLP/CB. Almost all of the 2',5'-dialkoxychalcones exhibited potent inhibitory effects on nitric oxide (NO) formation from murine microglial cell lines N9 stimulated with lipopolysaccharide (LPS). Of these, compound 11 showed the greatest effect (IC50=0.7+/-0.06 microM). The present results demonstrated that most of the chalcone derivatives have an anti-inflammatory effect. The inhibitory effects of dialkoxychalcones, 10-12 on inflammation are probably not due to the inhibition of mast cells and neutrophil degranulation, but are mediated through the suppression of NO formation from N9 cells.
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PMID:Synthesis and anti-inflammatory effect of chalcones. 1071 46

Nucleotide positions conserved on the 3' side of the initiator codon ATG and the corresponding N-terminal amino acid residues in a number of highly abundant plant proteins were identified by computational analysis of a dataset of highly expressed plant genes. The reporter genes uidA and gfp were modified to introduce these features. Insertion of GCT TCC TCC after the initiator codon ATG augmented expression for both the reporter genes. The insertion of each successive codon improved the expression of beta-glucuronidase (GUS) in an incremental fashion in transient transformation of tobacco (Nicotiana tabacum) leaves. The insertion of alanine-serine (Ser)-Ser resulted in about a 2-fold increase in the stability of GUS. However, this did not account for the 30- to 40-fold increase in GUS activity between the constructs coding for methionine-alanine-Ser-Ser-GUS and the native enzyme. Substitution of the codon for Ser at the third amino acid residue with synonymous codons reduced GUS expression. The results suggest a role for the conserved nucleotides in the +4 to +11 region in augmenting posttranscriptional events in the expression of genes in plants.
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PMID:Sequence architecture downstream of the initiator codon enhances gene expression and protein stability in plants. 1150 May 61

The anti-inflammatory activities of the isolated flavonoids, quercetin 3-O-methyl ether (1), kaempferol (2), and quercetin (3), of Rhamnus nakaharai, and anthraquinone, frangulin B (4), of Rhamnus formosana, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, macrophages, and microglial cells. Compounds 1 - 3 strongly inhibited the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Compound 1 strongly inhibited superoxide anion formation in fMLP/CB or phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils. Compound 1 exhibited potent inhibitory effect on tumor-necrosis factor-alpha ( TNF-alpha) formation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells while 1 and 4 showed potent inhibitory effects on TNF-alpha formation in LPS/IFN-gamma (interferon-gamma)-stimulated murine microglial cell lines N9.
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PMID:In vitro anti-inflammatory effects of quercetin 3-O-methyl ether and other constituents from Rhamnus species. 1173 18

Two new pentaoxygenated xanthones, 2,3-dihydroxy-1,6,7-trimethoxyxanthone (1) and 3,6-dihydroxy-1,5,7-trimethoxyxanthone (2) were isolated from the leaf of Hypericum geminiflorum. The antiplatelet activities of the constituents, 2,6-dimethoxy-p-benzoquinone (3), gemichalcone A (4), gemichalcone B (5), and cycloartocarpin (6), of this plant, were assessed in vitro by determining their inhibitory effects on the aggregation of washed rabbit platelets induced by various inducers. The anti-inflammatory effects of 4 and 5 were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells and neutrophils. Of the compounds tested, 4 exhibited the most potent inhibition of platelet aggregation induced by arachidonic acid (AA) and 4 and 5 strongly inhibited the release of beta-glucuronidase and lysozyme in formyl-Met-Leu-Phe (fMLP)-stimulated rat neutrophils.
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PMID:Antiplatelet and anti-inflammatory constituents and new oxygenated xanthones from Hypericum geminiflorum. 1184 22

Azurophil granules of neutrophils beyond their already known heterogeneity of beta-glucuronidase and myeloperoxidase enzyme contents are heterogeneous with respect to a spontaneous or low concentration (2.3 or 23 nM) of formyl-Met-Leu-Phe-induced mobilization. This suggests that the heterogeneity of azurophil granules is manifested in their functions too.
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PMID:Azurophil granules are heterogeneous with respect to mobilization induced by different concentrations of fMLP. 1185 80

Some chalcones exert potent anti-inflammatory activities. 2',5'-Dialkoxychalcones and 2',5'-dihydroxy-4-chloro-dihydrochalcone inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells and in LPS-activated RAW 264.7 macrophage-like cells have been demonstrated in our previous reports. These compounds also suppressed the inducible NO synthase (iNOS) expression and cyclooxygenase-2 (COX-2) activity in RAW 264.7 cells. In an effort to continually develop potent anti-inflammatory agent, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and then evaluated their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. Most of the 2',5'-dihydroxychaclone derivatives exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Some chalcones showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. Compounds 1 and 5 exhibited potent inhibitory effects on NO production in macrophages and microglial cells. Compound 11 showed inhibitory effect on NO production and iNOS protein expression in RAW 264.7 cells. The present results demonstrated that most of the 2',5'-dihydroxychaclones have anti-inflammatory effects. The potent inhibitory effect of 2',5'-dihydroxy-dihydrochaclones on NO production in LPS-activated macrophage, probably through the suppression of iNOS protein expression, is proposed to be useful for the relief of septic shock.
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PMID:Structure-activity relationship studies on chalcone derivatives. the potent inhibition of chemical mediators release. 1246 13


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