Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism
Fecha de publicación2012
Gonzalo Benito, Hugo
Cacabelos Barral, Daniel
Peralta Moncusí, Silvia
MetadatosMostrar el registro completo del ítem
Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals
(n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2α is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor γ (PPARγ). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS.
Es parte deJournal of Neurochemistry, 2012, vol. 123, núm. 4, p. 622-634
Showing items related by title, author, creator and subject.
Gonzalo Benito, Hugo; Nogueras, L.; Gil-Sánchez, Anna; Vicente Hervás, José; Valcheva, Petya; González Mingot, Cristina; Martin-Gari, Meritxell; Canudes, Marc; Peralta Moncusí, Silvia; Solana Moga, M. José; Pamplona Gras, Reinald; Portero Otín, Manuel; Boada Pallàs, Jordi; Serrano Casasola, José Carlos Enrique; Brieva Ruiz, Luis (Frontiers Media, 2019)Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and ...
Plant-derived phenolics inhibit the accrual of structurally characterised protein and lipid oxidative modifications Soler Cantero, Arantza; Jové Font, Mariona; Cacabelos Barral, Daniel; Boada Pallàs, Jordi; Naudí i Farré, Alba; Romero Fabregat, Mª Paz; Cassanyé, Anna; Serrano Casasola, José Carlos Enrique; Arola i Ferrer, Lluís; Valls, Josep; Bellmunt i Curcó, Josepa; Prat Corominas, Joan; Pamplona Gras, Reinald; Portero Otín, Manuel; Motilva Casado, Mª José (Public Library of Science, 2012)Epidemiological data suggest that plant-derived phenolics beneficial effects include an inhibition of LDL oxidation. After applying a screening method based on 2,4-dinitrophenyl hydrazine- protein carbonyl reaction to 21 ...
Lipid profile of cerebrospinal fluid in multiple sclerosis patients: a potential tool for diagnosis Nogueras, L.; Gonzalo Benito, Hugo; Jové Font, Mariona; Sol, Joaquim; Gil-Sanchez, A.; Hervás, J.V.; Valcheva, P.; González Mingot, Cristina; Solana Moga, M. José; Peralta Moncusí, Silvia; Pamplona Gras, Reinald; Brieva Ruiz, Luis (Nature Publishing Group, 2019-08-05)Multiple sclerosis (MS) is a complex multifactorial neuropathology. Although its etiology remains unclear, it has been demonstrated that the immune system attacks myelin, leading to demyelination and axonal damage. The ...