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Convergence of nitric oxide and lipid signaling: anti-inflammatory nitro-fatty acids

Baker, Paul R. S., Schopfer, Francisco J., O'Donnell, Valerie Bridget and Freeman, Bruce A. 2009. Convergence of nitric oxide and lipid signaling: anti-inflammatory nitro-fatty acids. Free Radical Biology & Medicine 46 (8) , pp. 989-1003. 10.1016/j.freeradbiomed.2008.11.021

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Abstract

The signaling mediators nitric oxide (˙NO) and oxidized lipids, once viewed to transduce metabolic and inflammatory information via discrete and independent pathways, are now appreciated as interdependent regulators of immune response and metabolic homeostasis. The interactions between these two classes of mediators result in reciprocal control of mediator sythesis that is strongly influenced by the local chemical environment. The relationship between the two pathways extends beyond coregulation of ˙NO and eicosanoid formation to converge via the nitration of unsaturated fatty acids to yield nitro derivatives (NO2-FA). These pluripotent signaling molecules are generated in vivo as an adaptive response to oxidative inflammatory conditions and manifest predominantly anti-inflammatory signaling reactions. These actions of NO2-FA are diverse, with these species serving as a potential chemical reserve of ˙NO, reacting with cellular nucleophiles to posttranslationally modify protein structure, function, and localization. In this regard these species act as potent endogenous ligands for peroxisome proliferator-activated receptor γ. Functional consequences of these signaling mechanisms have been shown in multiple model systems, including the inhibition of platelet and neutrophil functions, induction of heme oxygenase-1, inhibition of LPS-induced cytokine release in monocytes, increased insulin sensitivity and glucose uptake in adipocytes, and relaxation of preconstricted rat aortic segments. These observations have propelled further in vitro and in vivo studies of mechanisms of NO2-FA signaling and metabolism, highlighting the therapeutic potential of this class of molecules as anti-inflammatory drug candidates.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: nitrated fatty acids, nitric oxide, oxidized lipids, signal transduction, inflammation
Publisher: Elsevier
ISSN: 0891-5849
Last Modified: 04 Jun 2017 03:42
URI: http://orca.cf.ac.uk/id/eprint/25267

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