UNIPROT:P47989 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenolcarboxylic acids (caffeic acid, p-coumaric acid, ferulic acid) and their dehydrogenation polymer (DHP) were compared for their ability to inhibit the nitric oxide (NO) production by lipopolysaccharide (LPS)-activated mouse macrophage-like cells Raw 264.7 and to scavenge superoxide (O2-) (generated by hypoxanthine and xanthine oxidase reaction), hydroxyl radical (generated by Fenton reaction) and NO radical (generated by NOC-7), using ESR spectroscopy in vitro. All phenolcarboxylic acids effectively inhibited the NO production by activated Raw 264.7 cells. Among them, caffeic acid showed the highest cytotoxic activity, radical intensity and O2- scavenging activity, but the least NO scavenging activity. Caffeic acid also inhibited the NO production most effectively. Polymers of caffeic acid (DHP-CA) and p-coumaric acid (DHP-pCA) showed higher cytotoxicity, radical intensity and radical scavenging activity and more efficiently inhibited the NO production, as compared with the corresponding monomers. DHP-CA showed higher radical generation and O2- scavenging activity than DHP-pCA. The potent O2- scavenging activity of caffeic acid was probably due to the chemical reaction of O2- to the cathecol groups. Caffeic acid, DHP-CA and DHP-pCA induced the cytotoxicity, possibly due to autogenerating radicals, because these compounds efficiently produced radicals under alkaline conditions. In summary, caffeic acid acted as a polyphenolics in phenylcarboxylic acids. A possible link between cytotoxicity and radical generation of phenylcarboxylic acids is proposed.
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PMID:Inhibition of NO production by activated macrophages by phenolcarboxylic acid monomers and polymers with radical scavenging activity. 1282 Mar 89

The present study investigated the mechanisms involved in the increased 5-hydroxytryptamine (5-HT) vasoconstriction observed in rat middle cerebral arteries exposed in vitro to lipopolysaccharide (LPS, 10 microg x ml-1) for 1-5 h. Functional, immunohistochemical and Western blot analysis and superoxide anion measurements by ethidium fluorescence were performed. LPS exposure increased 5-HT (10 microm) vasoconstriction only during the first 4 h. In contrast to control tissue, indomethacin (10 microm), the COX-2 inhibitor NS 398 (10 microm), the TXA2/PGH2 receptor antagonist SQ 29548 (1 microm) and the TXA2 synthase inhibitor furegrelate (1 microm) reduced 5-HT contraction of LPS-treated arteries from hour one. The iNOS inhibitor aminoguanidine (0.1 mm) increased 5-HT contraction from hour three of LPS incubation. The superoxide anion scavenger superoxide dismutase (SOD, 100 U ml-1) and the H2O2 scavenger catalase (1000 U ml-1), as well as the respective inhibitors of NAD(P)H oxidase and xanthine oxidase, apocynin (0.3 mm) and allopurinol (0.3 mm), reduced 5-HT contraction after LPS incubation. LPS induced an increase in superoxide anion levels that was abolished by PEG-SOD. Subthreshold concentrations of the TXA2 analogue U 46619, xanthine/xanthine oxidase and H2O2 potentiated, whereas those of sodium nitroprusside inhibited, the 5-HT contraction. COX-2 expression was increased at 1 and 5 h of LPS incubation, while that of iNOS, Cu/Zn-SOD and Mn-SOD was only increased after 5 h. All the three vascular layers expressed COX-2 and Cu/Zn-SOD. iNOS expression was detected in the endothelium and adventitia after LPS. In conclusion, increased production of TXA2 from COX-2, superoxide anion and H2O2 enhanced vasoconstriction to 5-HT during the first few hours of LPS exposure; iNOS and SOD expression counteracted that increase at 5 h. These changes can contribute to the disturbance of cerebral blood flow in endotoxic shock.
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PMID:Mechanisms involved in the early increase of serotonin contraction evoked by endotoxin in rat middle cerebral arteries. 1453 51

To investigate the status of soluble adhesion molecules (sAMs) during aging, the present study determined protein levels of several major sAMs in serum samples obtained from rats at different ages. These sAMs include E-selectin, P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1). Fischer 344 rats, ages 6, 12, 18, and 24 months, fed ad libitum (AL) and calorie restricted (CR) diets were used in this study. Analysis by Western blotting showed that the levels of all sAMs studied increased during aging in AL rats, but were effectively blunted in the CR rats. Total reactive oxygen species/reactive nitrogen species (ROS/RNS) levels were measured by fluorescent probe 2',7'-dichlorofluorescin diacetate. Increased ROS/RNS levels were found to coincide with increased levels of superoxide-generating xanthine oxidase in serum during aging, but were found suppressed by CR. Increases in sAMs levels were duplicated in another experiment in which young (13-month-old) and old (31-month-old) rats were injected with proinflammatory lipopolysaccharide. These findings suggest that the altered expressions of sAMs may be due to increased oxidative stress with advanced age and that these increases were prevented by CR through its antioxidative action.
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PMID:Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction. 1468 95

This study investigated for the first time the effects of the cis isomer of resveratrol (c-RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)-2 and inducible cyclooxygenase (COX)-2. Treatment with 1-100 microM c-RESV significantly inhibited intracellular and extracellular ROS production, and c-RESV at 10-100 microM significantly reduced RNS production. c-RESV at 1-100 microM was ineffective for scavenging superoxide radicals (O(2)(.-)), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c-RESV at 10-100 microM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c-RESV at 100 microM decreased NOS-2 and COX-2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN-gamma)-treated macrophages. At 10-100 microM, c-RESV also significantly inhibited NOS-2 and COX-2 protein synthesis and decreased prostaglandin E(2) (PGE(2)) production. These results indicate that c-RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O(2)(.-)(-) and of the proinflammatory mediators NO(.-) and PGE(2)).
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PMID:Effects of cis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes. 1498 45

Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that regulates target gene transcription in a ligand-dependent manner. The in vivo effects of lipopolysaccharide (LPS) on expression of PXR and its target gene cytochrome P450 3A (CYP3A) in mouse liver were investigated in this study. Mice were injected intraperitoneally with different doses of LPS (0.1-5.0 mg/kg). PXR and CYP3A11 mRNA levels were measured using reverse transcription polymerase chain reaction. Results indicate that LPS significantly inhibits the expression of PXR mRNA in a dose-dependent manner, followed by suppression of CYP3A11 mRNA in mouse liver. LPS also represses the upregulation of CYP3A11 mRNA levels and erythromycin N-demethylase (ERND) catalytic activity in mice pretreated with PXR ligands dexamethasone, rifampicin, mifepristone, and phenobarbital. LPS-induced downregulation of PXR and CYP3A11 mRNA in liver was significantly attenuated in mice pretreated with gadolinium chloride, a selective Kupffer cell toxicant. Pretreatment with a single dose of gadolinium chloride (10 mg/kg) also significantly attenuated LPS-induced downregulation of dexamethasone-, rifampicim-, mifepristone-, and phenobarbital-inducible, CYP3A11 mRNA expression and ERND activity in mouse liver. Furthermore, LPS-induced downregulation of PXR and CYP3A11 mRNA was significantly attenuated in mice pretreated with allopurinol, an inhibitor of xanthine oxidase, and diphenyleneiodonium chloride, an inhibitor of NADPH oxidase. Allopurinol and diphenyleneiodonium chloride pretreatment also attenuated the repressive effects of LPS on dexamethasone-, rifampicin-, mifepristone-, and phenobarbital-inducible CYP3A11 mRNA expression and ERND catalytic activity in mouse liver. However, aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, has no effect on LPS-induced downregulation of PXR and CYP3A11 mRNA. Finally, LPS-induced downregulation of PXR and CYP3A11 mRNA was prevented in mice pretreated with either N-acetylcysteine or ascorbic acid. These antioxidants also prevented the repressive effects of LPS on dexamethasone-, rifampicin-, mifepristone-, and phenobarbital-inducible CYP3A11 mRNA expression and ERND catalytic activity in mouse liver. These results indicate that Kupffer cells contribute to LPS-induced downregulation of PXR and CYP3A in mouse liver. Reactive oxygen species, produced possibly by NADPH oxidase and perhaps by xanthine oxidase, are involved in LPS-induced downregulation of nuclear receptor PXR and its target gene CYP3A in mouse liver.
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PMID:Kupffer cells and reactive oxygen species partially mediate lipopolysaccharide-induced downregulation of nuclear receptor pregnane x receptor and its target gene CYP3a in mouse liver. 1518 91

The anti-oxidant effects of ethyl acetate (EAcE) and n-hexane extracts (nHE) of dried leaves of Stachytarpheta jamaicensis Vahl. (Verbenaceae) on the reactive oxygen species (ROS) generating during the respiratory burst of rat peritoneal macrophages were investigated. Only EAcE, at concentrations between 0.4 and 40 microg/ml, inhibited the extracellular release of oxygen radicals by resident peritoneal macrophages stimulated with phorbol-12-myristate 13-acetate (PMA). At concentrations above 40 microg/ml, EAcE inhibited the production of nitric oxide (NO) in macrophages stimulated in vivo with sodium thioglycollate then in vitro with lipopolysaccharide (LPS) and gamma-interferon (IFN-gamma). nHE extracts at concentrations between 0.4 and 40 microg/ml did not scavenge (O-)2 generated enzymatically by hypoxanthine/xanthine oxidase (HX/XO) system, but EAcE at the same concentrations showed potent (O-)2-scavenging activity. At 40 microg/ml, EAcE also inhibited XO activity. These results suggest that the EAcE extract of S. jamaicensis may be a potential pharmaceutical value in treatment of immunopathological diseases related to oxidative stress.
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PMID:Inhibitory effects of leaf extracts of Stachytarpheta jamaicensis (Verbenaceae) on the respiratory burst of rat macrophages. 1528 69

Reperfusion after cardiopulmonary bypass causes induction of reactive oxygen species (ROS), elevated plasma levels of bacterial lipopolysaccharide (LPS), and production of tumor necrosis factor-alpha (TNF) by the heart. Nuclear factor-kappaB (NF-kappaB) regulates the expression of TNF. Because NF-kappaB is activated by both LPS and ROS, we hypothesized that an inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), would block release of TNF from the heart stimulated by these two agents. With Institutional animal care and use committee (IACUC) approval, rat hearts were perfused Langendorf style. LPS was infused and ROS were generated with a hypoxanthine/xanthine oxidase system. PDTC was added to the perfusion buffer. Other hearts were treated with forskolin in order to elevate cyclic AMP. Timed collections of coronary effluent were made for the determination of coronary flow and measurement of TNF. LPS stimulated TNF release to a maximum of 2247 +/- 133 pg/min at 150 minutes. PDTC inhibited LPS-stimulated TNF release. For instance, at 150 minutes, LPS-stimulated TNF release was 449 +/- 49 pg/min with 100 microM PDTC and was 70 +/- 65 pg/mL with 250 microM PDTC (P < 0.05 vs LPS alone). ROS stimulated TNF release was 1494 +/- 130 pg/min at 150 minutes and was not affected by PDTC. Forskolin almost completely blocked TNF release stimulated by LPS or ROS. These data are consistent with the notion that inhibitors of NF-kappaB block cytokine production stimulated by some agents but not others.
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PMID:Regulation of tumor necrosis factor-alpha production in the isolated rat heart stimulated by bacterial lipopolysaccharide or reactive oxygen. 1548 Dec 97

The flower buds of Tussilago farfara L. (Compositae) have been traditionally used in Oriental medicine for the treatment of bronchitis and asthma. The extract of T. farfara was reported to exhibit antiinflammatory actions by inhibiting arachidonic acid metabolism and nitric oxide (NO) production in lipopolysaccharide-activated macrophages. In the present study, we investigated the effects of the ethyl acetate (EA) fraction on various types of neuronal cell damage induced in primary cultured rat cortical cells. Its antioxidant activities were also evaluated by cell-free bioassays. We found that the EA fraction potently inhibited the neuronal damage induced by arachidonic acid. We also found that it significantly attenuated the neuronal damage induced by spermine NONOate, a stable NO generator. In addition, it inhibited the A(beta(25-35))-induced neurotoxicity and glutamate- or N-methyl-D-aspartic acid-induced excitotoxicity. It was found that the oxidative neuronal damage induced by H2O2, xanthine/xanthine oxidase, or Fe(2+)/ascorbic acid was also inhibited by the EA fraction. Furthermore, it was shown to inhibit lipid peroxidation initiated by Fe(2+)/ascorbic acid in rat brain homogenates, and scavenge DPPH radicals. This is the first demonstration of neuroprotective and antioxidant effects of T. farfara. Although complex mechanisms may be involved in the neuroprotective actions, T. farfara may be useful for the management of neurodegenerative disorders associated with inflammation, A(beta), excitotoxicity, and/or oxidative stress.
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PMID:Neuroprotective and antioxidant effects of the ethyl acetate fraction prepared from Tussilago farfara L. 1574 68

Antimicrobial peptides (AMPs), in addition to their antibacterial properties, are also chemotactic and signalling molecules that connect the innate and adaptive immune responses. The role of AMP [alpha defensins, LL-37, a cathepsin G-derived peptide (CG117-136), protegrins (PG-1), polymyxin B (PMX) and LLP1] in modulating the respiratory burst response in human and murine macrophages in the presence of bacterial endotoxin [lipopolysaccharide (LPS) or lipooligosaccharide (LOS)] was investigated. AMP were found to neutralize endotoxin induction of nitric oxide and TNFalpha release in macrophages in a dose-dependent manner. In contrast, macrophages primed overnight with AMP and LOS or LPS significantly enhanced reactive oxygen species (ROS) release compared with cells primed with endotoxin or AMP alone, while no responses were seen in unprimed cells. This enhanced ROS release by macrophages was seen in all cell lines including those obtained from C3H/HeJ (TLR4-/-) mice. Similar effects were also seen when AMP and endotoxin were added directly with zymosan to trigger phagocytosis and the respiratory burst in unprimed RAW 264.7 and C3H/HeJ macrophages. Amplification of ROS release was also demonstrated in a cell-free system of xanthine and xanthine oxidase. Although AMP inhibited cytokine and nitric oxide induction by endotoxin in a TLR4-dependent manner, AMP and endotoxin amplified ROS release in a TLR4-independent manner possibly by exerting a prolonged catalytic effect on the ROS generating enzymes such as the NADPH-oxidase complex.
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PMID:Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophages. 1609 13

We previously conducted screening tests of the chloroform extracts from a total of 89 species of Japanese plant food items for their suppressive effects on superoxide (O(2) ()) generation through both NADPH oxidase and xanthine oxidase, and reported that mioga ginger (Zingiber mioga Roscoe) indicated the strongest suppressive activities. In this study, the suppressive effects of mioga ginger constituents, aframodial, and galanal B, together with [6]-gingerol and galanolactone occurring in ginger, on free radical generation and inducible proinflammatory gene expressions were investigated. Of these constituents, aframodial (20 microM) exhibited marked suppressive effects on 12-O-tetradecanoylphorbol-13-acetate-induced O(2) () generation in HL-60 cells and lipopolysaccharide (LPS)/interferon-gamma-induced nitric oxide (NO) generation in RAW264.7 cells (inhibition rates [IRs]=84.6% and 95.9%, respectively). Aframodial also strongly suppressed the stimulated HL-60 cell-induced mutagenicity in AS52 cells (IR=95.9%). The LPS-induced expression of inducible proinflammatory genes such as inducible NO synthase, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor was significantly abolished (IRs=99.1%, 74.6%, 74.0%, and 64.4%, respectively) by aframodial. In addition, degradation of the inhibitor of nuclear factor kappaB was suppressed by this compound (IR=100%), suggesting that the suppression of nuclear factor kappaB activation, at least in part, is involved. Taken together, these results suggest that aframodial has potent antioxidative and anti-inflammatory potentials, and may be a promising candidate in prevention and/or therapy for chronic inflammationassociated carcinogenesis.
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PMID:Suppressive effects of mioga ginger and ginger constituents on reactive oxygen and nitrogen species generation, and the expression of inducible pro-inflammatory genes in macrophages. 1635 25

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