title: Involvement of oxidative stress in occurrence of relapses in multiple sclerosis: the spectrum of oxidatively modified serum proteins detected by proteomics and redox proteomics analysis.
abstract: Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. Several evidences suggest that MS can be considered a multi-factorial disease in which both genetics and environmental factors are involved. Among proposed candidates, growing results support the involvement of oxidative stress (OS) in MS pathology. The aim of this study was to investigate the role of OS in event of exacerbations in MS on serum of relapsing-remitting (RR-MS) patients, either in relapsing or remitting phase, with respect to serum from healthy subjects. We applied proteomics and redox proteomics approaches to identify differently expressed and oxidatively modified proteins in the low-abundant serum protein fraction. Among differently expressed proteins ceruloplasmin, antithrombin III, clusterin, apolipoprotein E, and complement C3, were up-regulated in MS patients compared with healthy controls. Further by redox proteomics, vitamin D-binding protein showed a progressive trend of oxidation from remission to relapse, respect with controls. Similarly, the increase of oxidation of apolipoprotein A-IV confirmed that levels of OS are elevated with the progression of the disease. Our findings support the involvement of OS in MS and suggest that dysfunction of target proteins occurs upon oxidative damage and correlates with the pathology.
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Fiorini
authors.forename: Tatiana
authors.initials: T
authors.lastname: Koudriavtseva
authors.forename: Elona
authors.initials: E
authors.lastname: Bucaj
authors.forename: Raffaella
authors.initials: R
authors.lastname: Coccia
authors.forename: Cesira
authors.initials: C
authors.lastname: Foppoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giorgi
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.forename: Federico
authors.initials: F
authors.lastname: De Marco
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
mesh_terms: D000328:Adult; D001054:Apolipoproteins A / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D003710:Demography; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050050:Protein Carbonylation; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014809:Vitamin D-Binding Protein / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D001798:Blood Proteins; D014809:Vitamin D-Binding Protein; C022205:apolipoprotein A-IV