title: Lipoxidation adducts with peptides and proteins: deleterious modifications or signaling mechanisms?
abstract: Protein lipoxidation refers to the modification by electrophilic lipid oxidation products to form covalent adducts, which for many years has been considered as a deleterious consequence of oxidative stress. Oxidized lipids or phospholipids containing carbonyl moieties react readily with lysine to form Schiff bases; alternatively, oxidation products containing α,β-unsaturated moieties are susceptible to nucleophilic attack by cysteine, histidine or lysine residues to yield Michael adducts, overall corresponding to a large number of possible protein adducts. The most common detection methods for lipoxidized proteins take advantage of the presence of reactive carbonyl groups to add labels, or use antibodies. These methods have limitations in terms of specificity and identification of the modification site. The latter question is satisfactorily addressed by mass spectrometry, which enables the characterization of the adduct structure. This has allowed the identification of lipoxidized proteins in physiological and pathological situations. While in many cases lipoxidation interferes with protein function, causing inhibition of enzymatic activity and increased immunogenicity, there are a small number of cases where lipoxidation results in gain of function or activity. For certain proteins lipoxidation may represent a form of redox signaling, although more work is required to confirm the physiological relevance and mechanisms of such processes. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine.
authors.affiliation: Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address: mrd@ua.pt.
authors.forename: Rosário M
authors.initials: RM
authors.lastname: Domingues
authors.forename: Pedro
authors.initials: P
authors.lastname: Domingues
authors.forename: Tânia
authors.initials: T
authors.lastname: Melo
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez-Sala
authors.forename: Ana
authors.initials: A
authors.lastname: Reis
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Spickett
mesh_terms: D000818:Animals; D006801:Humans; D054878:Lipoylation / Q000502:physiology*; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012545:Schiff Bases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D010455:Peptides; D010743:Phospholipids; D012545:Schiff Bases
keywords: 1-palmitoyl-2-(5′-oxo)valeryl-sn-glycero-3 phosphorylcholine; 2,4-dinitrophenylhydrazine; 2,4-dinitrophenylhydrazone; 4-hydroxy-2-hexenal; 4-hydroxy-trans-2-nonenal; AANO2; Aldehydes; CID; DNP; DNPH; ESI; HHE; HNE; MALDI; MDA; MS/MS; Mass spectrometry; NO(2)-FAs; Nitro-fatty acids; OxPC; Oxidation; PG; POVPC; Prostaglandins; Protein–LPO; adducts of lipid peroxidation products with proteins; collision-induced dissociation; cyPG; cyclopentenone; electrospray ionization; malondialdehyde; matrix assisted laser desorption ionization; nitrated fatty acids; nitro-arachidonic acid; oxidation products of glycerophosphocholine; tandem mass spectrometry