Eosinophil Peroxidase Nitrates Protein Tyrosyl Residues

Wu, Weijia; Chen, Yonghong; Hazen, Stanley L.

doi:10.1074/jbc.274.36.25933

Cited by 251 publications

(82 citation statements)

References 64 publications

(49 reference statements)

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“…The pathways leading to the nitration of tyrosine residues in proteins have been extensively studied in vitro (19 -32). Biochemical reactions that have been shown to generate nitrating species include: (i) the reaction of superoxide with nitric oxide to generate peroxynitrite, which in turn may form more potent nitrating species by reaction with either CO 2 or metal (19, 28 -30); (ii) the oxidation of nitrite by peroxidases and H 2 O 2 (20,(23)(24)(25)(26)32); (iii) the acidification of nitrite; and (iv) the reaction of tyrosyl radical with nitric oxide or nitrogen dioxide (26,32). Recent studies utilizing mice with genetic deficiencies in myeloperoxidase (32)(33)(34) and eosinophil peroxidase (32) revealed a significant contribution of these two peroxidases in the extracellular nitration of proteins at sites of inflammation.…”

Section: Exposure Of Vascular Smooth Muscle Cells To Cytokines and LImentioning

confidence: 99%

Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells

Fries

Paxinou

Themistocleous

et al. 2003

Journal of Biological Chemistry

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A significant increase in the induction of inducible nitric-oxide synthase (iNOS) protein expression and in the levels of nitrite plus nitrate was observed in rat aortic smooth muscle cells (RASMCs) stably transfected with catalase (RASMC-2C2) as compared with empty vector-transfected RASMC-V4 cells after exposure to cytokines and lipopolysaccharide. The increased expression of iNOS protein in the RASMC-2C2 cells was associated with a significant activation of nuclear transcription factor B, one of the transcriptional regulators of iNOS expression. The induction of iNOS was also accompanied by increased protein tyrosine nitration in both cell types as revealed by immunocytochemical staining and high pressure liquid chromatography with on-line electrospray ionization tandem mass spectrometry. Nitrotyrosine formation was inhibited by 1400W, an iNOS inhibitor, by 4-(2-aminoethyl) benzenesulfonyl fluoride, an inhibitor of NADPH oxidase, and by the superoxide dismutase mimetic M40403, but not by the peroxidase inhibitor 4-aminobenzoic hydrazide. Electron microscopy using affinity-purified anti-nitrotyrosine antibodies revealed labeling at the cytosolic side of the rough endoplasmic reticulum membranes, in the nucleus, occasionally in mitochondria, and consistently within the fibrillar layer underneath the plasma membrane. Collectively, the data in this model system indicate that hydrogen peroxide, by inhibiting the activation of nuclear transcription factor B, prevents iNOS expression, whereas superoxide contributes in a precise pattern of intracellular protein tyrosine nitration.

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Section: Exposure Of Vascular Smooth Muscle Cells To Cytokines and LImentioning

confidence: 99%

Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells

Fries

Paxinou

Themistocleous

et al. 2003

Journal of Biological Chemistry

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“…In addition to a ONOO Ϫ -mediated pathway, NT formation has been shown to result from the catalysis of nitrite oxidation by peroxidases, thus providing an alternate mechanism for its formation in vivo (22)(23)(24). Although leukocyte peroxidases likely account for a substantial amount of NT production in vivo, this mechanism fails to explain NT formation in the absence of inflammatory cells or peroxidases [i.e., a MPO Ϫ/Ϫ mouse model (25)].…”

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confidence: 99%

Protein nitration is mediated by heme and free metals through Fenton-type chemistry: An alternative to the NO/O\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation}{\mathrm{_{2}^{-}}}\end{equation}\end{document} reaction

Thomas

Espey

Vitek

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

176

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The chemical origins of nitrated tyrosine residues (NT) formed in proteins during a variety of pathophysiological conditions remain controversial. Although numerous studies have concluded that NT is a signature for peroxynitrite (ONOO ؊ ) formation, other works suggest the primary involvement of peroxidases. Because metal homeostasis is often disrupted in conditions bearing NT, the role of metals as catalysts for protein nitration was examined. nitrotyrosine ͉ nitric oxide ͉ peroxynitrite ͉ oxidation ͉ hemin N itrated tyrosine residues (NT) have been used as a marker of the involvement of nitric oxide (NO) and its related chemistry in a number of pathophysiological disorders including cardiovascular (1, 2) neurodegenerative and malignant conditions (1-5), such as septic shock (6), multiple sclerosis (7), Alzheimer's disease (8), and amyotrophic lateral sclerosis (9). In cancer the presence of NT often correlates with a poor prognosis (10), suggesting diagnostic implications.Several mechanisms for NT formation have been proposed, and its origin remains controversial (11-16). Detection of NT in vitro following exposure to synthetic peroxynitrite (ONOO Ϫ ) initially suggested that the reaction of NO with superoxide (O 2 Ϫ ) may be the primary source of NT (17,18). Further studies demonstrated that cogeneration of NO and O 2 Ϫ gave dissimilar results than bolus synthetic ONOO Ϫ (12,19,20). These disparities in nitration yields arose from further reactions of ONOO Ϫ with excess NO or O 2 Ϫ (21). Given the complexity of this seemingly simple reaction, much debate has ensued over the likelihood of NT formation under biologically relevant conditions (12,14).In addition to a ONOO Ϫ -mediated pathway, NT formation has been shown to result from the catalysis of nitrite oxidation by peroxidases, thus providing an alternate mechanism for its formation in vivo (22-24). Although leukocyte peroxidases likely account for a substantial amount of NT production in vivo, this mechanism fails to explain NT formation in the absence of inflammatory cells or peroxidases [i.e., a MPO Ϫ/Ϫ mouse model (25)].NT has been shown to occur on distinct proteins rather than in an indiscriminate manner (26). This may result from variations in protein susceptibility to nitration due to conformational differences or to association with redox active metals (27,28). We evaluated the relative efficacy of the synthetic ONOO Ϫ , NO͞O 2 Ϫ cogeneration, peroxidase, and redox active metal pathways to promote NT formation. Materials and MethodsBSA (essentially globulin-free), ribonuclease A, ferriprotoporphyrin IX (hemin), superoxide dismutase (SOD; bovine erythrocytes), cytochrome c, horseradish peroxidase (HRP), catalase (Cat), hypoxanthine (HX), myoglobin (horse heart), 2,2Ј-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), FeSO 4 , diethylenetriaminepentaacetic acid (DTPA), dimethylformamide (DMF), ␤-amyloid (1-42) protein (A␤), MnO 2 , and CuCl 2 were purchased from Sigma-Aldrich. H 2 O 2 , NaHCO 3 , NaNO 2 , and FeCl 3 were from Fisher Scientific....

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“…Despite the proclivity of peroxidases to serve as initiators in the generation of reactive sulfur-derived species, we can find no reports of bisulfite oxidation mediated by any mammalian peroxidase. Eosinophil peroxidase (EPO) 3 is an abundant protein secreted from activated eosinophils (16 -18), white blood cells that play a central role in host defense mechanisms, allergic reactions, and asthma (19 -24 (12,(23)(24)(25). Studies thus far on EPO have focused primarily on its preference to oxidize these physiological substrates through a twoelectron oxidation pathway.…”

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“…Recently, it has been demonstrated that nitric oxide can serve as a substrate for EPO and compete with plasma levels of bromide, steering the enzyme reaction from a two-electron oxidation to a one-electron oxidation pathway by generation of reactive nitrogen species (25). In a model of nitrite oxidation (24), EPO has been reported to cause nitrotyrosine formation in vivo (26).…”

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confidence: 99%