Discovery of bioactive nitrated lipids and nitro-lipid-protein adducts using mass spectrometry-based approaches

Nitro-fatty acids (NO(2)-FA) undergo reversible Michael adduction reactions with cysteine and histidine residues leading to the post-translational modification (PTM) of proteins. This electrophilic character of NO(2)-FA is strictly related to their biological roles. The NO(2)-FA-induced PTM of signaling proteins can lead to modifications in protein structure, function, and subcellular localization. The nitro lipid-protein adducts trigger a series of downstream signaling events that culminates with anti-inflammatory, anti-hypertensive, and cytoprotective effects mediated by NO(2)-FA. These lipoxidation adducts have been detected and characterized both in model systems and in biological samples by using mass spectrometry (MS)-based approaches. These MS approaches allow to unequivocally identify the adduct together with the targeted residue of modification. The identification of the modified proteins allows inferring on the possible impact of the NO(2)-FA-induced modification. This review will focus on MS-based approaches as valuable tools to identify NO(2)-FA-protein adducts and to unveil the biological effect of this lipoxidation adducts.