Inducible nitric oxidase synthase

Shiloh, M.U., MacMicking, J.D., Nicholson, S., Brause, J.E., Potter, S., Marino, M., Fang, F., Dinauer, M., Nathan, C. Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase, Immunity 1999, 10, 29-38. 

Tricyclic thiopyran-2-one derivatives are useful in the development of therapies for the treatment of viral infections and diseases including AIDS <1996USP5504104>. The thiocoumarin 583 has been identified as a weak inhibitor of inducible nitric oxide synthase <2005BMC2723> and the (l,3,4-thiadiazol-5-yl)thiocoumarin 584 is active against monoamine oxidase B in rat brains <1994EPP594036>. 

Li J, Baud O, Vartanian T, Volpe JJ, Rosenberg PA (2005) Perox-initrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Proc Natl Acad Sci USA 102 9937-9941. 

In the production of injurious substances, i.e., oxidants, EM was proved to inhibit HADPH/NADH oxidase induction, resulting in the reduction of superoxide anion synthesis [26]. Sato etal. reported that EM exhibited an antioxidant effect in the influenza virus-infected mice model. Although mice infected with influenza virus usually die, EM dramatically improved the survival ratio of infected mice. This improvement is due to the antioxidant effect, which showed inhibition of IFN-y causing attenuation of inducible nitric oxide synthase (iNOS) transcription by erythromycin [95] (Fig. 18). 

On the other hand, it has been studied that some PPGs affects the expression or activation of endogen enzymes that produce free radicals, like xanthine oxidase [72, 82] or inducible nitric oxide synthase [56], But, the PPGs assayed (2-acetylverbascoside, cistanoside, echinacoside, forsythoside... 

Fig 24.23. A model for the role of ROS and RNOS in neuronal degradation in Parkinson s disease. 1. Dopamine levels are reduced by monoamine oxidase, which generates H2O2. 2. Superoxide also can be produced by mitochondria, which SOD will convert to H2O2. Iron levels increase, which allows the Fenton reaction to proceed, generating hydroxyl radicals. 3. NO, produced by inducible nitric oxide synthase, reacts with superoxide to form RNOS. 4. The RNOS and hydroxyl radical lead to radical chain reactions that result in Upid peroxidation, protein oxidation, the formation of lipofuscin, and neuronal degeneration. The end result is a reduced production and release of dopamine, which leads to the clinical symptoms observed. 

The major oxidative or nitrosative stress in tumours probably arises from infiltrating macrophages, which can produce both superoxide and nitric oxide radicals [38,39] via an NADPH-oxidase and inducible nitric oxide synthase (NOS) respectively. NOS activity is elevated in some common tumours compared to adjacent, normal tissue [40,41], and the implications of nitric oxide production in cancer therapy have been reviewed [42,43]. (NOS is a flavoprotein which can also reduce oxygen to superoxide if the normal substrate (L-arginine) is depleted [44].)... 

Brennan, R. E RusseU, K., Zhang, G and Samuel, J. E. (2004) Both inducible nitric oxide synthase and NADPH oxidase contribute to the control of virulent phase I Coxiella burnetii infections. Infect. Itrwiun. 72, 6666-6675. 

Cyclooxygenase-2 Inducible nitric oxide synthase Xanthine oxidase... 

Ungvari Z, Csiszar A, Edwards JG, et al. Increased superoxide production in coronary arteries in hyperhomocysteinemia role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase. A/tenoscfer Thromb Vase Biol 2003 23 418-424. 

EGCG and theaflavins were found to inhibit xanthine oxidase (12,14) and suppress the production of ROS in HL-60 cells (12). EGCG and theaflavins inhibit nitric oxide production, which appears to be mediated through suppression of inducible nitric oxide synthase (iNOS), as demonstrated by its mRNA and protein levels (15,16). Electrophoretic mobility shift assay revealed that theaflavins and EGCG blunted activation of NFkB responsible for iNOS induction (15). These results indicate that these tea polyphenols inhibit the binding of NF /c B to iNOS promoter, thereby suppressing the transcription of iNOS gene. 

Kozlovski, V.I., Olszanecki, R., and Chlopicki, S. 2006. Free radicals generated by xan-thine/xanthine oxidase system augment nitric oxide synthase (NOS) and cyclooxygenase (COX)-independent component of bradykinin-induced vasodilatation in the isolated guinea pig heart. Pharmacol. Rep. 58 405—412. 

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