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Nitrated unsaturated fatty acids, such as 10- and 12-nitrolinoleic acid (LNO2), cholesteryl nitrolinoleate, and nitrohydroxylinoleate, represent a new class of endogenous lipid-derived signalling molecules. LNO2 isomers serve as potent endogenous ligands for PPARγ and can also decompose or be metabolized to release nitric oxide.1,2,3,4 10-Nitrooleic acid is one of two regioisomers of nitrooleic acid, the other being 9-nitrooleic acid (OA-NO2; used for the mixture of isomers), which are formed by nitration of oleic acid in approximately equal proportions in vivo.5 Peroxynitrite, acidified nitrite, and myeloperoxidase in the presence of H2O2 and nitrite, all mediate the nitration of oleic acid. OA-NO2 is found in human plasma as the free acid and esterified in phospholipids at concentrations of 619 ± 52 nM and 302 ± 369 nM, respectively. OA-NO2 activates PPARγ approximately 7-fold at a concentration of 1 µM and effectively promotes differentiation 3T3-L1 preadipocytes to adipocytes at 3 µM.5
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1
Lim, D.G., Sweeney, S., Bloodsworth, A., et al. Nitrolinoleate, a nitric oxide-derived mediator of cell function: Synthesis, characterization, and vasomotor activity. Proc Natl Acad Sci USA 99(25) 15941-15946 (2002).
2
Schopfer, F.J., Lin, Y., Baker, P.R.S., et al. Nitrolinoleic acid: An endogenous peroxisome proliferator-activated receptor g ligand. Proc Natl Acad Sci USA 102(7) 2340-2345 (2005).
3
Lima, E.S., Bonini, M.G., Augusto, O., et al. Nitrated lipids decompose to nitric oxide and lipid radicals and cause vasorelaxation. Free Radic Biol Med 39 532-539 (2005).
4
Baker, P.R.S., Schopfer, F.J., Sweeney, S., et al. Red cell membrane and plasma linoleic acid nitration products: Synthesis, clinical identification, and quantitation. Proc Natl Acad Sci USA 101(32) 11577-11582 (2004).
5
Baker, P.R., Lin, Y., Schopfer, F.J., et al. Fatty acid transduction of nitric oxide signaling. Multiple nitrated unsaturated acid derivatives exist in human blood and urine serve as endogenous peroxisome proliferator-activated receptor ligands. J Biol Chem 280(51) 42464-42475 (2005).
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