The mechanism of oleic acid nitration by •NO2

Nitrooleic Acid, an Endogenous Product of Nitrative Stress, Activates Nociceptive Sensory Nerves via the Direct Activation of TRPA1

“…RNS are potent inflammatory molecules that can react with lipids, proteins, and DNA (Szabó et al, 2007). Within membranes, where the hydrophobic environment maximizes RNS production (Möller et al, 2007), RNS react with unsaturated fatty acids (e.g., oleic acid), causing the addition of an NO 2 group (nitration) Jain et al, 2008;Trostchansky and Rubbo, 2008). Nitrated fatty acids (e.g., nitrooleic acid) are highly reactive electrophilic compounds that can modulate a variety of cellular targets, including thiol residues and peroxisome proliferator-activated receptor ␥ Trostchansky and Rubbo, 2008 ABBREVIATIONS: NOS, nitric-oxide synthase; ROS, reactive oxygen species; RNS, reactive nitrogen species; OA, oleic acid; OA-NO 2 , nitrooleic acid; 4HNE, 4-hydroxynonenal; TRP, transient receptor potential; AITC, allyl isothiocyanate; HEK, human embryonic kidney; FBS, fetal bovine serum; AM, acetyoxymethyl ester; HC030031, 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; 4ONE, 4-oxononenal; PTIO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; DTT, dithiothreitol; PGA 2 , prostaglandin A 2 ; carboxyPTIO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; SIN-1, 3-morpholino-sydnonimine; AP-18, 4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime; hTRPA1-HEK, HEK cells stably transfected with human TRPA1 channels; hTRPV1-HEK, HEK cells stably transfected with human TRPV1 channels.…”

“…RNS are potent inflammatory molecules that can react with lipids, proteins, and DNA (Szabó et al, 2007). Within membranes, where the hydrophobic environment maximizes RNS production (Möller et al, 2007), RNS react with unsaturated fatty acids (e.g., oleic acid), causing the addition of an NO 2 group (nitration) Jain et al, 2008;Trostchansky and Rubbo, 2008). Nitrated fatty acids (e.g., nitrooleic acid) are highly reactive electrophilic compounds that can modulate a variety of cellular targets, including thiol residues and peroxisome proliferator-activated receptor ␥ Trostchansky and Rubbo, 2008).…”

“…Nitrated fatty acids are detectable in vitro after exposure of fatty acids to RNS donors (O'Donnell et al, 1999;Jain et al, 2008). Nitrated fatty acids have been measured in human plasma and red blood cells, with total nitrooleic acid (OA-NO 2 ) and total nitrolinoleic acid concentrations in plasma of 920 and 630 nM, respectively .…”

Trends in the Evaluation of Lipid Peroxidation Processes

“…The nitro-fatty acids have distinct bioactivities from their precursor lipids [Baker et al, 2009;Freeman et al, 2008;Kim et al, 2005;Lee et al, 2008;White et al, 2010]. Studies identified a high number of nitro-fatty acid species and proved an elevated formation of RNS in hydrophobic environments, such as the lipid bilayer, suggesting that lipids might constitute candidates for nitrosative signal transduction [Jain et al, 2008;Moller et al, 2005;Moller et al, 2007;Thomas et al, 2001].…”

Nitrosative modifications of protein and lipid signaling molecules by reactive nitrogen species

“…Lipid reactions with RNS can result in the formation of cis or trans nitro-alkanes, where the NO 2 group is present at the site of the double bond, as well as nitro-hydroxy and nitro-hydroperoxy lipids (6). Multiple unsaturated fatty acids including oleate, linoleate and arachidonate have been shown to have nitro-derivatives (54,125,133). Importantly, the high number of nitro-fatty acid species identified to date likely represents the elevated formation of RNS in hydrophobic environments, such as the lipid bilayer, which inherently makes lipids excellent candidates for nitrosative signal transduction (31,75,80,81,122).…”