Cited by 201Antioxidant Activity and Oxidative StressNitric Oxide and Endothelin EffectsRedox biology and oxidative stress

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

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Baker, Paul R. S., Schopfer, Francisco J., Sweeney, Scott, Freeman, Bruce A.·2004·Proceedings of the National Academy of Sciences

Abstract

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 [ 13 C]LNO 2 as an internal standard, red cell free and esterified LNO 2 content was 50 ± 17 and 249 ± 104 nM, respectively. The free and esterified LNO 2 content of plasma was 79 ± 35 and 550 ± 275 nM, respectively. Nitrated fatty acids, thus, represent the single largest pool of bioactive oxides of nitrogen in the vasculature, with a net LNO 2 concentration of 477 ± 128 nM, excluding buffy coat cells. These observations affirm that basal oxidative and nitrating conditions occur in healthy humans to an extent that is sufficient to induce abundant membrane and lipoprotein–fatty acid nitration. Given that LNO 2 is capable of mediating cGMP and non-cGMP-dependent signaling reactions, fatty acid nitration products are species representing the convergence of NO and oxygenated lipid cell-signaling pathways.

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  • Peroxynitrite can mediate lipid nitration.

    “For example, lipids are also a significant biological target for peroxynitrite, and although the species can abstract a hydrogen atom to initiate lipid peroxidation, a detrimental process that can lead to cytotoxicity in many cases (65, 766), peroxynitrite can also mediate lipid nitration (54, 1027).”
  • Nitrated fatty acids have been detected both in animal tissues subjected to inflammatory conditions and endogenously in healthy human plasma and urine.

    “Nitrated fatty acids have been detected both in animal tissues subjected to inflammatory conditions and endogenously in healthy human plasma and urine (25,38).”

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  1. [22]Lim, D. G., Sweeney, S., Bloodsworth, A., White, C. R., Chumley, P. H., Krishna, N. R., Schopfer, F., O'Donnell, V. B., Eiserich, J. P. & Freeman, B. A. (2002) Proc. Natl. Acad. Sci. USA 99, 15941-15946.
  2. [33]Gladwin, M. T., Shelhamer, J. H., Schechter, A. N., Pease-Fye, M. E., Waclawiw, M. A., Panza, J. A., Ognibene, F. P. & Cannon, R. O., III. (2000) Proc. Natl. Acad. Sci. USA 97, 11482-11487.

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Authors
Baker, P. R. S., Schopfer, F. J., Sweeney, S., & Freeman, B. A.
Affiliations
  • University of Alabama at Birmingham (US)
  • University of California, Los Angeles (US)
  • Departments of Anesthesiology, Biochemistry, and Molecular Genetics and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294
Venue
Proceedings of the National Academy of Sciences
Published
2004-07-23
Volume
101
Issue
32
Pages
11577-11582
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2137704083
Cited by
201
References
44
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 4 · 2013: 12 · 2012: 13
FWCI
8.62
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wake Forest University
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL64937, R01HL064937, R01HL058115, R01-HL-58115, T32-HL-07457, T32HL007457)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
nitrated fatty acids, plasma lipids, nitric oxide metabolites, nitric oxide, esterified fatty acids, regioisomers, 13C-labeled internal standards, lipid oxidation, signal transduction, cGMP signaling, nitrosation
MeSH terms
Chromatography, High Pressure Liquid, Erythrocyte Membrane, Fatty Acids, Unsaturated, Humans, Isomerism, Nitro Compounds, Mass Spectrometry, Linoleic Acid

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