The Experts below are selected from a list of 26133 Experts worldwide ranked by ideXlab platform
Toshio Hattori - One of the best experts on this subject based on the ideXlab platform.
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Xanthine oxidase inhibition reduces Reactive Nitrogen Species production in COPD airways
The European respiratory journal, 2003Co-Authors: Masakazu Ichinose, Akira Koarai, Hisatoshi Sugiura, M. Tomaki, Yuichi Komaki, Kunio Shirato, S Yamagata, Hiromasa Ogawa, Peter J. Barnes, Toshio HattoriAbstract:Reactive Nitrogen Species (RNS) have been reported to be involved in the inflammatory process in chronic obstructive pulmonary disease (COPD). However, there are no studies on the modulation of RNS in COPD. It was hypothesised that inhibition of xanthine oxidase (XO) might decrease RNS production in COPD airways through the suppression of superoxide anion production. Ten COPD and six healthy subjects participated in the study. The XO inhibitor allopurinol (300 mg x day(-1) p.o. for 4 weeks) was administered to COPD patients. RNS production in the airway was assessed by 3-nitrotyrosine immunoreactivity and enzymic activity of XO in induced sputum as well as by exhaled nitric oxide (eNO) concentration. XO activity in the airway was significantly elevated in COPD compared with healthy subjects. Allopurinol administration to COPD subjects significantly decreased XO activity and nitrotyrosine formation. In contrast, eNO concentration was significantly increased by allopurinol administration. These results suggest that oral administration of the xanthine oxidase inhibitor allopurinol reduces airway Reactive Nitrogen Species production in chronic obstructive pulmonary disease subjects. This intervention may be useful in the future management of chronic obstructive pulmonary disease.
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iNOS depletion completely diminishes Reactive Nitrogen-Species formation after an allergic response
The European respiratory journal, 2002Co-Authors: Akira Koarai, Masakazu Ichinose, Hisatoshi Sugiura, M. Tomaki, M. Watanabe, Shunsuke Yamagata, Yuichi Komaki, Kunio Shirato, Toshio HattoriAbstract:Nitric oxide (NO) shows proinflammatory actions mainly via Reactive Nitrogen Species (RNS) formation through superoxide- and peroxidase-dependent mechanisms. The purpose of this study was to examine the role of inducible NO synthase (iNOS) in RNS production, airway hyperresponsiveness, and inflammation after allergen challenge. Ovalbumin (OVA)-sensitised, iNOS-deficient and wild-type mice were used. RNS production was assessed by nitrotyrosine (NT) immunoreactivity in the airways. Airway inflammation and responsiveness were evaluated by eosinophil accumulation and methacholine (i.v.) challenge, respectively. In wild-type mice, OVA-inhalation challenge increased iNOS immunoreactivity in airway epithelial cells as well as iNOS protein measured by Western blotting. The total amounts of nitrite and nitrate in bronchoalveolar lavage (BAL) fluid were increased, and NT immunoreactivity was also observed abundantly in airway inflammatory cells. In iNOS-deficient mice, both iNOS expression and NT formation were completely abolished, and the total amounts of nitrite and nitrate in BAL fluid were significantly decreased. In contrast, OVA-induced airway eosinophil recruitment and hyperresponsiveness were observed almost equally in wild-type and iNOS-deficient mice. These data suggest that Reactive Nitrogen Species production after allergic reaction occurs totally via inducible nitric oxide synthase-dependent pathways. Allergen-mediated airway eosinophil recruitment and hyperresponsiveness appear to be independent of Reactive Nitrogen Species production.
C S Raine - One of the best experts on this subject based on the ideXlab platform.
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cytokine localization in multiple sclerosis lesions correlation with adhesion molecule expression and Reactive Nitrogen Species
Neurology, 1995Co-Authors: C F Brosnan, B Cannella, L Battistini, C S RaineAbstract:The relative levels and cellular distribution of proinflammatory and regulatory cytokines have been examined by immunohistochemistry in multiple sclerosis (MS) lesions of differing activity and compared with CNS tissue from other neurologic diseases with an inflammatory or noninflammatory component.Results show widespread distribution of cytokines in association with both perivascular inflammatory cells and glial cells in all types of inflammatory lesions. Although no obvious pattern of proinflammatory versus regulatory cytokines could be determined in MS lesions, proinflammatory cytokines were rarely noted in normal and noninflammatory conditions, whereas regulatory cytokines were readily detectable in the same diseases. The possible relevance of these cytokine patterns to adhesion molecule expression and the presence of Reactive Nitrogen Species is also addressed. NEUROLOGY 1995;45(Suppl 6): S16-S21
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Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and Reactive Nitrogen Species.
Neurology, 1995Co-Authors: C F Brosnan, B Cannella, L Battistini, C S RaineAbstract:The relative levels and cellular distribution of proinflammatory and regulatory cytokines have been examined by immunohistochemistry in multiple sclerosis (MS) lesions of differing activity and compared with CNS tissue from other neurologic diseases with an inflammatory or noninflammatory component. Results show widespread distribution of cytokines in association with both perivascular inflammatory cells and glial cells in all types of inflammatory lesions. Although no obvious pattern of proinflammatory versus regulatory cytokines could be determined in MS lesions, proinflammatory cytokines were rarely noted in normal and noninflammatory conditions, whereas regulatory cytokines were readily detectable in the same diseases. The possible relevance of these cytokine patterns to adhesion molecule expression and the presence of Reactive Nitrogen Species is also addressed.
Glyn B. Steventon - One of the best experts on this subject based on the ideXlab platform.
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post translational activation of human phenylalanine 4 monooxygenase from an endobiotic to a xenobiotic enzyme by Reactive oxygen and Reactive Nitrogen Species
Xenobiotica, 2010Co-Authors: A Antypa, C Rebello, Adriana Biernacka, K Krajewski, J Cassam, S. C. Mitchell, Glyn B. SteventonAbstract:An investigation into the post-translational activation of cDNA-expressed human phenylalanine 4-monooxygenase and human hepatic cytosolic fraction phenylalanine 4-monooxygenase activity with respect to both endobiotic metabolism and xenobiotic metabolism revealed that the Reactive oxygen Species (hydrogen peroxide and hydroxyl radical) and Reactive Nitrogen Species (nitric oxide and peroxynitrite) could elicit the post-translational activation of the enzyme with respect to both of these biotransformation reactions.In virtually all instances, the Km values were decreased and the Vmax values were increased; the only exceptions observed being with hydrogen peroxide and L-phenylalanine.These effects were shown to occur at activator concentrations known to exist in physiological situations and, hence, suggest that Reactive oxygen and Reactive Nitrogen Species may cause, and may be involved with, the post-translational activation of phenylalanine 4-monooxygenase within the human body.This mechanism, in response...
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Post-translational activation of human phenylalanine 4-monooxygenase from an endobiotic to a xenobiotic enzyme by Reactive oxygen and Reactive Nitrogen Species
Xenobiotica; the fate of foreign compounds in biological systems, 2010Co-Authors: A Antypa, C Rebello, Adriana Biernacka, K Krajewski, J Cassam, S. C. Mitchell, Glyn B. SteventonAbstract:An investigation into the post-translational activation of cDNA-expressed human phenylalanine 4-monooxygenase and human hepatic cytosolic fraction phenylalanine 4-monooxygenase activity with respect to both endobiotic metabolism and xenobiotic metabolism revealed that the Reactive oxygen Species (hydrogen peroxide and hydroxyl radical) and Reactive Nitrogen Species (nitric oxide and peroxynitrite) could elicit the post-translational activation of the enzyme with respect to both of these biotransformation reactions. In virtually all instances, the K(m) values were decreased and the V(max) values were increased; the only exceptions observed being with hydrogen peroxide and L-phenylalanine. These effects were shown to occur at activator concentrations known to exist in physiological situations and, hence, suggest that Reactive oxygen and Reactive Nitrogen Species may cause, and may be involved with, the post-translational activation of phenylalanine 4-monooxygenase within the human body. This mechanism, in response to free-radical bursts, may enable the enzyme to expand its substrate range and to process certain xenobiotics as and when required.
Hiroshi Ohshima - One of the best experts on this subject based on the ideXlab platform.
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Nitration and nitrosation of N-acetyl-L-tryptophan and tryptophan residues in proteins by various Reactive Nitrogen Species.
Free radical biology & medicine, 2004Co-Authors: Toshinori Suzuki, Howard F. Mower, Marlin D. Friesen, Isabelle Gilibert, Tomohiro Sawa, Hiroshi OhshimaAbstract:Proteins are targets of Reactive Nitrogen Species such as peroxynitrite and Nitrogen dioxide. Among the various amino acids in proteins, tryptophan residues are especially susceptible to attack by Reactive Nitrogen Species. We carried out experiments on the reactions of peroxynitrite and other Reactive Nitrogen Species with N-acetyl-l-tryptophan under various conditions. Four major products were identified as 1-nitroso-N-acetyl-l-tryptophan, 1-nitro-N-acetyl-l-tryptophan, 6-nitro-N-acetyl-l-tryptophan, and N-acetyl-N′-formyl-l-kynurenine on the basis of their mass and UV spectra. The reactions with SIN-1 (a peroxynitrite generator), Angeli's salt (a nitroxyl donor), and spermine NONOate (a nitric oxide donor) generated the nitroso derivative but not the nitro derivatives. A myeloperoxidase–H2O2–NO2− system generated the nitro derivatives but not the nitroso derivative. Under physiological conditions 6-nitro-N-acetyl-l-tryptophan was stable, whereas the 1-nitroso and 1-nitro derivatives decomposed with half-lives of 1.5 and 18 h, respectively. After treatment with various Reactive Nitrogen Species, bovine serum albumin was enzymatically hydrolyzed and analyzed for 6-nitro-l-tryptophan and 3-nitro-l-tyrosine by HPLC with electrochemical detection. Levels of 6-nitro-l-tryptophan and 3-nitro-l-tyrosine were similar in the nitrated protein. 6-Nitro-l-tryptophan in proteins can be measured as an additional biomarker of protein nitration.
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Formation of 8-nitroguanosine in cellular RNA as a biomarker of exposure to Reactive Nitrogen Species.
Chemico-biological interactions, 2002Co-Authors: Mitsuharu Masuda, Hoyoku Nishino, Hiroshi OhshimaAbstract:Reactive Nitrogen Species, such as peroxynitrite, Nitrogen oxides and nitryl chloride, have been implicated as a cause of diverse pathophysiological conditions, including inflammation, neurodegenerative and cardiovascular diseases and cancer. We previously reported that 8-nitroguanine is formed by reactions of guanine or calf-thymus DNA with peroxynitrite in vitro. In the present study, we have studied the formation of 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine in reactions of calf-liver RNA with various Reactive Nitrogen Species. 8-Nitroguanosine in RNA was found to be much more stable than 8-nitro-2' -deoxyguanosine in DNA, which rapidly depurinates to release 8-nitroguanine. Both 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine were formed in calf-liver RNA following exposure to various Reactive Nitrogen Species, such as synthetic peroxynitrite. They were also formed in RNA by Reactive Species formed from nitric oxide and superoxide anion generated concomitantly from 3-morpholino-sydnonimine (SIN-1) and those formed with myeloperoxidase or horseradish peroxidase in the presence of nitrite and hydrogen peroxide. 8-Nitroguanosine was detected by HPLC with an electrochemical detector in enzymatic hydrolyzates of RNA isolated from human lung carcinoma cells incubated with synthetic peroxynitrite. Our results indicate that 8-nitroguanosine in cellular RNA could be measured as a marker of damage caused by endogenous Reactive Nitrogen Species in tissues and cells.
Wook Song - One of the best experts on this subject based on the ideXlab platform.
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Specificity of antioxidant enzyme inhibition in skeletal muscle to Reactive Nitrogen Species donors.
Biochemical and biophysical research communications, 2002Co-Authors: John M. Lawler, Wook SongAbstract:Abstract Nitric oxide ( NO ) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by Reactive Nitrogen Species (RNS), including NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: NO donor); (b) 0, 100, 500 μM , or 1 mM sodium nitroprusside (SNP: NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: NO donor); or (d) 0 or 500 μM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 μM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that Reactive Nitrogen Species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
