Fatty acid transduction of nitric oxide signaling: Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor

Francisco J. Schopfer, Paul R.S. Baker, Gregory Giles, Phil Chumley, Carlos Batthyany, Jack Crawford, Rakesh P. Patel, Neil Hogg, Bruce Branchaud, Jack R. Lancaster, Bruce A. Freeman

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

The aqueous decay and concomitant release of nitric oxide (.NO) by nitrolinoleic acid (10-nitro-9,12-octadecadienoic acid and 12-nitro-9,12-octadecadienoic acid; LNO2) are reported. Mass spectrometric analysis of reaction products supports a modified Nef reaction as the mechanism accounting for the generation of .NO by the aqueous reactions of fatty acid nitroalkene derivatives. Nitrolinoleic acid is stabilized by an aprotic milieu, with LNO2 decay and .NO release strongly inhibited by phosphatidylcholine/cholesterol liposome membranes and detergents when present at levels above their critical micellar concentrations. The release of .NO from LNO2 was induced by UV photolysis and triiodide-based ozone chemiluminescence reactions currently used to quantify putative protein nitrosothiol and N-nitrosamine derivatives. This reactivity of LNO2 complicates the qualitative and quantitative analysis of biological oxides of nitrogen when applying UV photolysis and triiodide-based analytical systems to biological preparations typically abundant in nitrated fatty acids. The results reveal that nitroalkene derivatives of linoleic acid are pluripotent signaling mediators that act not only via receptor-dependent mechanisms, but also by transducing the signaling actions of .NO via pathways subject to regulation by the relative distribution of LNO2 to hydrophobic versus aqueous microenvironments.

Original languageEnglish (US)
Pages (from-to)19289-19297
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number19
DOIs
StatePublished - May 13 2005
Externally publishedYes

Fingerprint

Nitric Oxide Donors
Nitric Oxide
Fatty Acids
Photolysis
Derivatives
Nitrogen Oxides
Nitrosamines
Chemiluminescence
Ozone
Linoleic Acid
Luminescence
Phosphatidylcholines
Reaction products
Liposomes
Detergents
Cholesterol
Membranes
Chemical analysis
10-nitro-9,12-octadecadienoic acid
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Schopfer, F. J., Baker, P. R. S., Giles, G., Chumley, P., Batthyany, C., Crawford, J., ... Freeman, B. A. (2005). Fatty acid transduction of nitric oxide signaling: Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor. Journal of Biological Chemistry, 280(19), 19289-19297. https://doi.org/10.1074/jbc.M414689200

Fatty acid transduction of nitric oxide signaling : Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor. / Schopfer, Francisco J.; Baker, Paul R.S.; Giles, Gregory; Chumley, Phil; Batthyany, Carlos; Crawford, Jack; Patel, Rakesh P.; Hogg, Neil; Branchaud, Bruce; Lancaster, Jack R.; Freeman, Bruce A.

In: Journal of Biological Chemistry, Vol. 280, No. 19, 13.05.2005, p. 19289-19297.

Research output: Contribution to journalArticle

Schopfer, FJ, Baker, PRS, Giles, G, Chumley, P, Batthyany, C, Crawford, J, Patel, RP, Hogg, N, Branchaud, B, Lancaster, JR & Freeman, BA 2005, 'Fatty acid transduction of nitric oxide signaling: Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor', Journal of Biological Chemistry, vol. 280, no. 19, pp. 19289-19297. https://doi.org/10.1074/jbc.M414689200
Schopfer, Francisco J. ; Baker, Paul R.S. ; Giles, Gregory ; Chumley, Phil ; Batthyany, Carlos ; Crawford, Jack ; Patel, Rakesh P. ; Hogg, Neil ; Branchaud, Bruce ; Lancaster, Jack R. ; Freeman, Bruce A. / Fatty acid transduction of nitric oxide signaling : Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 19. pp. 19289-19297.
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