Nitrolinoleate, a nitric oxide-derived mediator of cell function: Synthesis, characterization, and vasomotor activity

Lim, Dong Gun; Sweeney, Scott; Bloodsworth, Allison; White, C. Roger; Chumley, Phillip; Krishna, N. Rama; Schöpfer, Francisco J.; O'Donnell, Valerie Bridget; Eiserich, Jason P.; Freeman, Bruce Α.

doi:10.1073/pnas.232409599

Cited by 106 publications

(101 citation statements)

References 59 publications

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“…For example, nitrolinoleate is capable of inhibiting platelet and neutrophil function by a cAMP-dependent process (for example, (127)). Also, nitrolinoleate can serve as a storage form of · NO since chemical decomposition releases · NO and elicits vasorelaxation (128). Nitro derivatives of oleic acid have also been found to be capable of eliciting gene expression via activation of PPAR-gamma (126).…”

Section: B Fatty Acid Nitrationmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

219

165

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During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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Section: B Fatty Acid Nitrationmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

219

165

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“…4A) increased the purity and yield of fatty acid allylic nitration products significantly, facilitating the structural resolution of specific LNO 2 positional isomers (22,31,32). Preparative TLC permitted the initial resolution of nitrated fatty acids from starting materials and oxidized linoleic acid species (Fig.…”

Section: Synthesis Of Lno2mentioning

confidence: 99%

“…4B). These changes in synthetic approaches increased linoleic acid nitration product yield from 4% to Ͼ50% (22).…”

Section: Synthesis Of Lno2mentioning

confidence: 99%

“…Acid-catalyzed fatty acid nitration is expected during physiological and pathological conditions in which NO 2 Ϫ is exposed to low pH (e.g., pH Ͻ 4.0), such as in the gastric compartment after endosomal or phagolysosomal acidification or in tissues after postischemic reperfusion. Nitrated linoleic acid (LNO 2 ) ‡ displays robust cell-signaling activities that appear to be antiinflammatory (20,(22)(23)(24)(25). LNO 2 inhibits platelet function by means of cAMP-dependent mechanisms (26), and it inhibits neutrophil O 2…”

mentioning

confidence: 99%

“…LNO 2 also induces vessel relaxation, in part by means of cGMP-dependent mechanisms (22,27). In aggregate, these data infer that nitrated unsaturated fatty acids represent a class of lipid-derived signaling mediators.…”

mentioning

confidence: 99%

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Red cell membrane and plasma linoleic acid nitration products: Synthesis, clinical identification, and quantitation

Baker

Schöpfer

Sweeney

et al. 2004

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

Self Cite

192

191

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Nitric oxide ( • NO) and its reactive metabolites mediate the oxidation, nitration, and nitrosation of DNA bases, amino acids, and lipids. Here, we report the structural characterization and quantitation of two allylic nitro derivatives of linoleic acid (LNO 2), present as both free and esterified species in human red cell membranes and plasma lipids. The LNO 2 isomers 10-nitro-9-cis,12-cis-octadecadienoic acid and 12-nitro-9-cis,12-cis-octadecadienoic acid were synthesized and compared with red cell and plasma LNO 2 species based on chromatographic elution and mass spectral properties. Collision-induced dissociation fragmentation patterns from synthetic LNO 2 isomers were identical to those of the two most prevalent LNO 2 positional isomers found in red cells and plasma. By using • NO exerts a particularly broad influence on oxidative inflammatory reactions by reacting at diffusion-limited rates with superoxide ( • O 2 Ϫ , k ϭ 1.9 ϫ 10 10 M Ϫ1 ⅐sec Ϫ1 ) to yield peroxynitrite (ONOO Ϫ ) and its conjugate acid, peroxynitritrous acid (ONOOH), the latter of which undergoes homolytic scission to nitrogen dioxide ( • NO 2 ) and hydroxyl radical ( • OH) (2, 6). Also, biological conditions favor the reaction of ONOO Ϫ with CO 2 , generating nitrosoperoxycarbonate (ONO-OCO 2 Ϫ ; k ϭ 3 ϫ 10 4 M Ϫ1 ⅐sec Ϫ1 ), which yields • NO 2 and carbonate ( • CO 3 Ϫ ) radicals by means of homolysis or rearranges to NO 3 Ϫ and CO 2 (7). During inflammation, neutrophil myeloperoxidase and heme proteins, such as myoglobin and cytochrome c, form H 2 O 2 -dependent Compound I intermediates that are direct oxidants and catalyze the consumption of • NO and the oxidation of nitrite (NO 2 Ϫ ) to • NO 2 (8-11). Although the rate of reaction of • NO with O 2 is slow (k ϭ 2 ϫ 10 6 M Ϫ2 ⅐sec Ϫ1 ), the small molecular radius, uncharged nature, and lipophilicity of • NO and O 2 facilitate their diffusion and concentration in membranes and lipoproteins up to 20-fold (12-14). This ''molecular lens'' effect that is induced by solvation in hydrophobic cell compartments accelerates the reaction of • NO with O 2 to yield N 2 O 3 and N 2 O 4 . As a consequence of this diversity of • NO reactions with partially reduced oxygen species, a rich spectrum of products is formed that orchestrates target molecule oxidation, nitrosation, and nitration reactions.Multiple mechanisms account for the nitration of fatty acids by• NO-derived species (15)(16)(17)(18)(19)(20). During both basal cell-signaling and tissue-inflammatory conditions, • NO 2 that is generated by the aforementioned reactions can react with membrane and lipoprotein lipids. Environmental sources also yield • NO 2 as a product of combustion.• NO 2 initiates autooxidation of polyunsaturated fatty acids by means of hydrogen abstraction from the bis-allylic carbon, to form nitrous acid and a resonance-stabilized allylic radical (21). This lipid radical species predominantly reacts with molecular oxygen to form a peroxyl radical. During the unique oxidationreduction conditions of inflammation or ischemia-...

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Lipid Peroxidation and Nitration

Davies¹,

Guo²

2013

Molecular Basis of Oxidative Stress

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Nitrolinoleate, a nitric oxide-derived mediator of cell function: Synthesis, characterization, and vasomotor activity

Cited by 106 publications

References 59 publications

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Red cell membrane and plasma linoleic acid nitration products: Synthesis, clinical identification, and quantitation

Lipid Peroxidation and Nitration

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