Formation of Nitrating and Chlorinating Species by Reaction of Nitrite with Hypochlorous Acid

Eiserich, Jason P.; Cross, Carroll E.; Jones, A. Daniel; Halliwell, Barry; Vliet, Albert van der

doi:10.1074/jbc.271.32.19199

Cited by 424 publications

(240 citation statements)

References 62 publications

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“…Definitive identification can be obtained by the use of HPLC separation combined with mass spectral identification (e.g. [133]) and co-elution. This has been done in some (e.g.…”

Section: Features Of Radical-mediated Protein Fragmentation and Polymmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,549

982

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Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

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“…Definitive identification can be obtained by the use of HPLC separation combined with mass spectral identification (e.g. [133]) and co-elution. This has been done in some (e.g.…”

Section: Features Of Radical-mediated Protein Fragmentation and Polymmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,549

982

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“…Myeloperoxidase Generates 3-Nitrotyrosine by Directly Oxidizing NO 2 Ϫ -It has been proposed that myeloperoxidase uses at least two distinct pathways to generate reactive nitrogen species (37). In the first pathway, the enzyme uses H 2 O 2 and Cl Ϫ to generate HOCl, which then reacts with NO 2 Ϫ to form nitryl chloride, a nitrating species.…”

Section: Myeloperoxidase Generates 3-nitrotyrosine In Hdl Protein Undmentioning

confidence: 99%

“…Because NO 2 Ϫ is a substrate for myeloperoxidase and other peroxidases, it might also be used to nitrate tyrosine in vivo (35,36). Indeed, myeloperoxidase uses H 2 O 2 and NO 2 Ϫ to generate reactive nitrogen species that nitrate free and proteinbound tyrosine residues and promote lipid peroxidation of LDL in vitro (37)(38)(39)(40). These reactions might be physiologically relevant because tyrosine nitration is markedly impaired in a model of peritoneal inflammation in myeloperoxidase-deficient mice by a reaction pathway that appears to require NO 2 Ϫ or other intermediates derived from NO (41).…”

mentioning

confidence: 99%

Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species

Pennathur

Bergt

Shao

et al. 2004

Journal of Biological Chemistry

255

230

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High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but itis not yet established whether HDL proteins are damaged by reactive nitrogen species in the circulation or artery wall. One pathway that generates such species involves myeloperoxidase (MPO), a major constituent of artery wall macrophages. Another pathway involves peroxynitrite, a potent oxidant generated in the reaction of nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine in vitro. To investigate the involvement of reactive nitrogen species in atherogenesis, we quantified 3-nitrotyrosine levels in HDL in vivo. The mean level of 3-nitrotyrosine in HDL isolated from human aortic atherosclerotic intima was 6-fold higher (619 ؎ 178 mol/mol Tyr) than that in circulating HDL (104 ؎ 11 mol/mol Tyr; p < 0.01). Immunohistochemical studies demonstrated striking colocalization of MPO with epitopes reactive with an antibody to 3-nitrotyrosine. However, there was no significant correlation between the levels of 3-chlorotyrosine, a specific product of MPO, and those of 3-nitrotyrosine in lesion HDL. We also detected 3-nitrotyrosine in circulating HDL, and linear regression analysis demonstrated a strong correlation between the levels of 3-chlorotyrosine and levels of 3-nitrotyrosine. These observations suggest that MPO promotes the formation of 3-chlorotyrosine and 3-nitrotyrosine in circulating HDL but that other pathways also produce 3-nitrotyrosine in atherosclerotic tissue. Levels of HDL isolated from plasma of patients with established coronary artery disease contained twice as much 3-nitrotyrosine as HDL from plasma of healthy subjects, suggesting that nitrated HDL might be a marker for clinically significant vascular disease. The detection of 3-nitrotyrosine in HDL raises the possibility that reactive nitrogen species derived from nitric oxide might promote atherogenesis. Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation.

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“…Peroxynitrite is formed in the reaction between nitric oxide (NO ⅐ ) and superoxide. Recently, however, other mechanisms for the production of nitrotyrosine that are independent of peroxynitrite have been identified (16,17), raising doubts about the specificity of nitrotyrosine detection as an assay for peroxynitrite (18).…”

mentioning

confidence: 99%

Nitric Oxide Trapping of the Tyrosyl Radical of Prostaglandin H Synthase-2 Leads to Tyrosine Iminoxyl Radical and Nitrotyrosine Formation

Gunther¹,

Hsi²,

Curtis³

et al. 1997

Journal of Biological Chemistry

162

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The determination of protein nitrotyrosine content has become a frequently used technique for the detection of oxidative tissue damage. Protein nitration has been suggested to be a final product of the production of highly reactive nitrogen oxide intermediates (e.g. peroxynitrite) formed in reactions between nitric oxide (NO ⅐ ) and oxygen-derived species such as superoxide. The enzyme prostaglandin H synthase-2 (PHS-2) forms one or more tyrosyl radicals during its enzymatic catalysis of prostaglandin formation. In the presence of the NO ⅐ -generator diethylamine nonoate, the electron spin resonance spectrum of the PHS-2-derived tyrosyl radical is replaced by the spectrum of another free radical containing a nitrogen atom. The magnitude of the nitrogen hyperfine coupling constant in the latter species unambiguously identifies it as an iminoxyl radical, which is likely formed by the oxidation of nitrosotyrosine, a stable product of the addition of NO ⅐ to tyrosyl radical. Addition of superoxide dismutase did not alter the spectra, indicating that peroxynitrite was not involved. Western blot analysis of PHS-2 after exposure to the NO ⅐ -generator revealed nitrotyrosine formation. The results provide a mechanism for nitric oxide-dependent tyrosine nitration that does not require formation of more highly reactive nitrogen oxide intermediates such as peroxynitrite or nitrogen dioxide.

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Formation of Nitrating and Chlorinating Species by Reaction of Nitrite with Hypochlorous Acid

Cited by 424 publications

References 62 publications

Biochemistry and pathology of radical-mediated protein oxidation

Biochemistry and pathology of radical-mediated protein oxidation

Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species

Nitric Oxide Trapping of the Tyrosyl Radical of Prostaglandin H Synthase-2 Leads to Tyrosine Iminoxyl Radical and Nitrotyrosine Formation

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