Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism
Autor: | Franz Tatzber, Cristina González, Hugo Gonzalo, Luis Brieva, Manuel Portero-Otin, Mariona Jové, Lourdes Hernández, Jordi Boada, Daniel Cacabelos, Silvia Peralta, Reinald Pamplona, Anna Cassanyé, José C. E. Serrano, Lucia Lanau-Angulo |
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Rok vydání: | 2012 |
Předmět: |
Adult
Male Multiple Sclerosis Population Peroxisome proliferator-activated receptor Biology Protein oxidation Biochemistry Mass Spectrometry Protein Carbonylation Lipid peroxidation Cellular and Molecular Neuroscience chemistry.chemical_compound Mucoproteins Metabolomics Malondialdehyde Lipidomics Humans education Chromatography High Pressure Liquid Autoantibodies Cell Line Transformed chemistry.chemical_classification education.field_of_study Fatty Acids Methylglyoxal Glyoxal Middle Aged Lipidome Pyruvaldehyde Lipids Molecular biology Lipoproteins LDL PPAR gamma chemistry Female Lipid Peroxidation Metabolic Networks and Pathways |
Zdroj: | Journal of Neurochemistry. 123:622-634 |
ISSN: | 0022-3042 |
Popis: | 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. |
Databáze: | OpenAIRE |
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