Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Gonzalo Benito, Hugo; Brieva Ruiz, Luis; Tatzber, Franz; Jové Font, Mariona; Cacabelos Barral, Daniel; Cassanyé, Anna; Lanau, Lucia; Boada Pallàs, Jordi; Serrano Casasola, José Carlos Enrique; González Mingot, Cristina; Hernández, Lourdes; Peralta Moncusí, Silvia; Pamplona Gras, Reinald; Portero Otín, Manuel

doi:https://doi.org/10.1111/j.1471-4159.2012.07934.x

Ver/Abrir

018290.pdf (568.9Kb)
Sol·licita una còpia

Fecha de publicación

2012

Autor/a

Gonzalo Benito, Hugo

Brieva Ruiz, Luis

Tatzber, Franz

Jové Font, Mariona

Cacabelos Barral, Daniel

Cassanyé, Anna

Lanau, Lucia

Boada Pallàs, Jordi

Serrano Casasola, José Carlos Enrique

González Mingot, Cristina

Hernández, Lourdes

Peralta Moncusí, Silvia

Pamplona Gras, Reinald

Portero Otín, Manuel

Cita recomendada

Gonzalo Benito, Hugo; Brieva Ruiz, Luis; Tatzber, Franz; Jové Font, Mariona; Cacabelos Barral, Daniel; Cassanyé, Anna; ... Portero Otín, Manuel. (2012) . Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism. Journal of Neurochemistry, 2012, vol. 123, núm. 4, p. 622-634. https://doi.org/10.1111/j.1471-4159.2012.07934.x.

Resumen

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.

URI

http://hdl.handle.net/10459.1/58574

DOI

https://doi.org/10.1111/j.1471-4159.2012.07934.x

Es parte de

Journal of Neurochemistry, 2012, vol. 123, núm. 4, p. 622-634