Electrophilic lipids, a new molecular tool in the treatment of inflammatory process?

BONACCI G

Buenos Aires

Congreso; VIII Internacional Congress of Society for Free Radical Biology and Medicine (SFRBM)-South American Grup (SAG).; 2013

Society for Free Radical Biology and Medicine (SFRBM)-South American Grup (SAG)

Unsaturated fatty acids modulate numerous signaling pathways involved in cellular homeostasis and metabolism. In particular, the oxidation or nitration through enzymatic or radical reactions results in the formation of lipid-derived electrophiles. These products of oxidative inflammatory reactions play an important role modulating the inflammatory process. The concentration, localization and type of electrophiles formed will determine either protective and anti-oxidant cellular responses or cytotoxic effects. In this regard, nitro-fatty acids (NO2-FA), the product of the reaction of nitric oxide-derived species and unsaturated fatty acids, have recently shown protective effects in several animal models of disease. Nitrated-fatty acids exhibit a particular electrophilic reactivity via Michael addition with biological nucleophiles, mainly critical cysteines in target proteins to impact structure and function. NO2-FA exerts its activity by adducting to transcriptional regulators such as PPAR, Keap1/Nrf2 and NF-B to control numerous genes involved in anti-oxidant, anti-inflammatory and cytoprotective events. Moreover, this broad reactivity and their desirable effects shown are related to the pluripotent actions displayed by electrophilic lipid in several acute and chronic animal models of disease, including diabetes, atherosclerosis, lung and cardiovascular disease.