Modification of cysteine residues by cyclopentenone prostaglandins in the elucidation of redox regulation of protein function

1 p. 52nd Congress of the European Societies of Toxicology (EUROTOX) Fibes Congress Center Seville, Spain, 04th-07th september 2016Cyclopentenone prostaglandins (cyPG) are electrophilic lipid mediators that are generated in increased amounts in situations associated with inflammation and oxidative stress. They can act as agonists of certain membrane and nuclear receptors and have been reported to play a role in lipid metabolism and regulation of inflammation. CyPG possess an α,β-unsaturated carbonyl group in the cyclopentenone ring, for which they can suffer the nucleophilic attack from certain residues in proteins and form covalent adducts through Michael addition. In this sense, they can serve as models for the action of other lipid electrophiles. The effects of cyPG are complex and depend on their levels and the presence of protein targets and context factors. Since the main nucleophiles involved in covalent adduct formation with cyPG are cysteine residues, there is a bidirectional interplay between cyPG addition and redox regulation. On one hand, the redox state of the cysteine residues will affect their availability for modification by cyPG. On the other hand, cyPG can modulate cellular redox status through their interactions with glutathione and redox-regulating enzymes and transcription factors. To get insight into these relationships, in recent years we have undertaken the identification of targets for modification by cyPG. Among the targets studied are Ras proteins, the cytoskeletal protein vimentin and enzymes of the family of aldo-keto reductases. These studies have helped unveil additional sites for redox and electrophilic regulation of protein function, as well as novel features of cyPG–protein interactions.SAF2015-68590-R (MINECO/FEDER), EU Project 675132 (H2020-MSCA-ITN-2015), RETIC RIRAAF RD12/0013/0008 (ISCIII, Spain).Peer reviewe