Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated. Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma. Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy. In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung. These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase. In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses. On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice.
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PMID:Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. 863 94

Nitric oxide release is induced in many cells, including vascular endothelium, as part of the host response to inflammation. Nitric oxide synthase activity is increased in patients with sepsis, associated with increased oxidant demands and decreased antioxidant protection. We used a human vascular endothelial cell line to investigate the influence of antioxidants on nitric oxide synthase activity. Cells were cultured to confluence and incubated with interferon gamma, tumor necrosis factor, and lipopolysaccharide in the combined presence of the antioxidants ascorbic acid, Trolox, catalase, or superoxide dismutase, singly and in combination, for 48 h. Additionally, some cells were incubated with hypoxanthine-xanthine oxidase or a nitric oxide donor. Nitric oxide synthase activity was upregulated by cytokine exposure (p < .0005). Ascorbic acid and superoxide dismutase/ catalase resulted in decreased enzyme activity (p < .05). Superoxide anion release from xanthine oxidase caused increased activity (p < .05) and exogenous nitric oxide tended to suppress synthase activity. We suggest that antioxidants scavenge superoxide anion, enabling feedback inhibition of nitric oxide synthase activity by nitric oxide, and thus reducing enzyme activity. Exogenous nitric oxide also has a similar effect. Superoxide generation suppresses this feedback inhibition. This study has important implications in patients with sepsis in whom nitric oxide synthase inhibitor therapy is currently under investigation.
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PMID:Regulation of nitric oxide synthase activity in cultured human endothelial cells: effect of antioxidants. 879 Oct 97

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