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)

Nitric oxide (NO) has cytotoxic effects but NO producing neurons are resistant to NO toxicity. These results suggest the presence of self-protecting factors for NO toxicity. Recently, 6R-tetrahydrobiopterin (6R-BH4), a cofactor for NO synthase (NOS), has been reported to degrade NO raising the possibility that 6R-BH4 acts as a self-protecting factor for NO toxicity. In PC12 cells which have NOS, three-day culture with sodium nitroprusside (SNP) or NOC-12, NO generators, at 10-100 microM increased nitrite and nitrate concentrations in the culture medium and induced death of PC12 cells. Coadministration of 6R-BH4 (10 or 30 microM) with SNP or NOC-12 prevented cell death with reduction of nitrite and nitrate in the medium. Inhibition of 6R-BH4 synthesis by 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor for GTP cyclohydrolase I, decreased cellular 6R-BH4 content and viable cell number. The inhibiting effects of DAHP were restored by exogenous 6R-BH4. NOS activity, as estimated by nitrite concentrations in the medium, was unchanged by DAHP. Hypoxanthine and xanthine oxidase, which produce superoxide, mimicked the cell-protecting effect of 6R-BH4 which is reported to generate superoxide during its autoxidation. These results suggest that 6R-BH4 acts as a self-protecting factor for NO toxicity with generation of superoxide in NO-producing neurons.
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PMID:Self-protection of PC12 cells by 6R-tetrahydrobiopterin from nitric oxide toxicity. 984 57

To test whether exogenous oxidants alter intracellular oxidant levels in skeletal muscle fibres, we exposed rat diaphragm to donors of nitric oxide (NOx), reactive oxygen species (ROS) or hyperoxia, and monitored intracellular oxidant levels using a fluorescent probe. Fibre bundles were dissected from the diaphragm and loaded with 2', 7'-dichlorodihydrofluorescein (DCFH); emissions were monitored using a fluorescence microscope. DCFH-loaded muscles were exposed to either a NOx donor (1 mM S-nitroso-N-acetyl penicillamine, SNAP; 1 mM sodium nitroprusside, SNP; 400 microM 1-hydroxy-2-oxo-3-(N-3-methyl-aminopropyl)-3-methyl-1-triazen, NOC-7), an ROS donor (100 microM hydrogen peroxide, H2O2; 100 microM tert-butyl hydroperoxide; 1 mM hypoxanthine plus 0.01 U mL-1 xanthine oxidase, HXXO) or a range of PO2s (25, 60 or 95% O2 oxygenating Krebs-Ringer solution) for 40 min; time-matched control bundles remained in Krebs-Ringer solution. Control muscles oxidized DCFH at a rate of 0.32 +/- 0.1 greyscale units min-1. SNAP (766%), SNP (1244%), NOC-7 (851%), H2O2 (543%), and HXXO (541%) increased DCFH oxidation from control levels. The increase in emissions caused by NOC-7 and SNP were blunted by the NOx scavenger haemoglobin (1 microM). DCFH oxidation by HXXO was unaffected by 1000 U mL-1 superoxide dismutase but was significantly decreased by 1000 U mL-1 catalase and 1 mM salicylate. PO2 had no effect on intracellular oxidant levels. Therefore, extracellular NOx and ROS can alter intracellular oxidant status in skeletal muscle fibres. These observations suggest that intrafibre oxidant levels could be the result of both intracellular and extracellular oxidant production.
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PMID:Exogenous reactive oxygen and nitric oxide alter intracellular oxidant status of skeletal muscle fibres. 1038 90

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

Hypoxia induces angiogenesis, partly through stabilization of hypoxia-inducible factor-1alpha (HIF-1alpha), leading to transcription of pro-angiogenic factors. Here we examined the regulation of HIF-1alpha by hypoxia and nitric oxide (NO) in explants of human cerebrovascular smooth muscle cells. Cells were treated with NO donors under normoxic or hypoxic (2% O2) conditions, followed by analysis of HIF-1alpha protein levels. Treatment with the NO donor sodium nitroprusside reduced levels of HIF-1alpha, whereas NO donors, NOC-18 and S-nitrosoglutathione, increased HIF-1alpha levels. SIN-1, which releases both NO and superoxide (O2*-), reduced HIF-1alpha levels, suggesting that inhibitory NO donors may elicit effects through peroxynitrite (ONOO*-). O2*- generation by xanthine/xanthine oxidase also reduced HIF-1alpha levels, confirming an inhibitory role for reactive oxygen species (ROS). Furthermore, superoxide dismutase increased HIF-1alpha levels, and the NO scavenger carboxy-PTIO reversed HIF-1alpha stabilization by NO donors. Effects on HIF-1alpha levels correlated with vascular endothelial growth factor transcription but did not affect HIF-1alpha transcription, as measured by RT-PCR and luciferase-reporter assays. The results indicate that HIF-1alpha is stabilized by agents that produce NO and reduce ROS but destabilized by agents that increase ROS, including O2*- and ONOO*-. Thus we propose that the effect of NO on HIF-1alpha signaling is critically dependent on the form of NO and the physiological environment of the responding cell.
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PMID:Nitric oxide and reactive oxygen species exert opposing effects on the stability of hypoxia-inducible factor-1alpha (HIF-1alpha) in explants of human pial arteries. 1465 4