Regulation of arachidonic acid oxidation and metabolism by lipid electrophiles.

Trostchansky, Andrés; Wood, Irene; Rubbo, Homero

Arachidonic acid (AA) is a precursor of enzymatic and non-enzymatic oxidized products such as prostaglandins, thromboxanes, leukotrienes, lipoxins, and isoprostanes. These products may exert signaling or damaging roles during physiological and pathological conditions, some of them being markers of oxidative stress linked to inflammation. Recent data support the concept that cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 (CYP450) followed by cytosolic and microsomal dehydrogenases can convert AA to lipid-derived electrophiles (LDE). Lipid-derived electrophiles are fatty acid derivatives bearing an electron-withdrawing group that can react with nucleophiles at proteins, DNA, and small antioxidant molecules exerting potent signaling properties. This review aims to describe the formation, sources, and electrophilic anti-inflammatory actions of key mammalian LDE.