title: Fatty acid transduction of nitric oxide signaling. Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor.
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.
authors.affiliation: Department of Anesthesiology and Center for Free Radical Biology, University of Alabama at Birmingham, Alabama 35294, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
authors.forename: Paul R S
authors.initials: PR
authors.lastname: Baker
authors.forename: Gregory
authors.initials: G
authors.lastname: Giles
authors.forename: Phil
authors.initials: P
authors.lastname: Chumley
authors.forename: Carlos
authors.initials: C
authors.lastname: Batthyany
authors.forename: Jack
authors.initials: J
authors.lastname: Crawford
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: Neil
authors.initials: N
authors.lastname: Hogg
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Branchaud
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lancaster
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
mesh_terms: D000818:Animals; D002621:Chemistry / Q000379:methods; D002784:Cholesterol / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D006736:Horses; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008041:Linoleic Acids / Q000737:chemistry*; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D008823:Micelles; D008956:Models, Chemical; D009211:Myoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D009574:Nitro Compounds / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry; D009602:Nitrosamines / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D015398:Signal Transduction; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: C501855:10-nitro-9,12-octadecadienoic acid; C501856:12-nitro-9,12-octadecadienoic acid; D003902:Detergents; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles; D009211:Myoglobin; D009574:Nitro Compounds; D009602:Nitrosamines; D010713:Phosphatidylcholines; D013438:Sulfhydryl Compounds; C027369:octadecadienoic acid; D009569:Nitric Oxide; D002784:Cholesterol; D009584:Nitrogen; D010100:Oxygen