title: Nitroproteomics of peripheral blood mononuclear cells from patients and a rat model of ALS.
abstract: Increased levels of 3-nitrotyrosine in the central nervous system have been found in patients and mouse models of familial ALS (fALS), suggesting a possible use of nitrated proteins as biomarkers. We analyzed peripheral blood mononuclear cells (PBMCs), easily accessible samples, from sporadic ALS (sALS) patients and a rat model of fALS (a) to establish whether an increased level of nitrated proteins was present in PBMCs, too, and (b) to identify possible candidate biomarkers. With a proteomic approach, we identified for the first time the major overnitrated proteins in PBMCs from patients and rats at different disease stages. In the rats, their increased levels already were measured at a presymptomatic stage. Among them, actin, ATP synthase, and vinculin overlap between sALS patients and the rat model. Interestingly, in a previous study, actin and ATPase have been found overnitrated in the spinal cord of a mouse model of fALS before disease onset, suggesting their possible involvement in motor neuron degeneration. In conclusion, we observed that an increased level of nitrated proteins was not restricted to the spinal cord but also was present in peripheral cells of patients and an animal model, and that nitrated proteins are promising candidate biomarkers for early diagnosis of ALS.
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nardo
authors.forename: Silvia
authors.initials: S
authors.lastname: Pozzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Mantovani
authors.forename: Silvia
authors.initials: S
authors.lastname: Garbelli
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Marinou
authors.forename: Manuela
authors.initials: M
authors.lastname: Basso
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.forename: Caterina
authors.initials: C
authors.lastname: Bendotti
authors.forename: Valentina
authors.initials: V
authors.lastname: Bonetto
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C002744:3-nitrotyrosine; D014443:Tyrosine