title: Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly.
abstract: Protein lipoxidation was assessed in the parietal cortex (PC), frontal cortex (FC), and cingulate gyrus (CG) in middle-aged and old-aged individuals with no clinical manifestations of cognitive impairment, in order to increase understanding of regional brain vulnerability to oxidative damage during aging. Twenty-five lipoxidized proteins were identified in all the three regions although with regional specificities, by using redox proteomics to detect target proteins of neuroketals (NKT) adduction. The number of cases with NKT-adducted proteins was higher in old-aged individuals but most oxidized proteins were already present in middle-aged individuals. Differences in vulnerability to oxidation were dependent on the sub-cellular localization, secondary structure, and external exposition of certain amino acids. Lipoxidized proteins included those involved in energy metabolism, cytoskeleton, proteostasis, neurotransmission and O2/CO2, and heme metabolism. Total NKT and soluble oligomer levels were estimated employing slot-blot, and these were compared between age groups. Oligomers increased with age in PC and FC; NKT significantly increased with age in FC, whereas total NKT and oligomer levels were not modified in CG, thus highlighting differences in brain regional vulnerability with age. Oligomers significantly correlated with NKT levels in the three cortical regions, suggesting that protein NKT adduction parallels soluble oligomer formation.
authors.affiliation: Institute of Neuropathology, University Hospital of Bellvitge, IDIBELL (Biomedical Research Institute of Bellvitge), Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain. Electronic address: mdominguezg@idibell.cat.
authors.forename: Mayelín
authors.initials: M
authors.lastname: Domínguez
authors.affiliation: Proteomics Platform, Barcelona Science Park, 08028 Barcelona, Spain. Electronic address: eoliveira@pcb.ub.es.
authors.forename: Eliandre
authors.initials: E
authors.lastname: de Oliveira
authors.affiliation: Proteomics Platform, Barcelona Science Park, 08028 Barcelona, Spain. Electronic address: maodena@pcb.ub.es.
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Odena
authors.affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, 25198 Lleida, Spain. Electronic address: manuel.portero@mex.udl.cat.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero
authors.affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, 25198 Lleida, Spain. Electronic address: reinald.pamplona@mex.udl.cat.
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.affiliation: Institute of Neuropathology, University Hospital of Bellvitge, IDIBELL (Biomedical Research Institute of Bellvitge), Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain; Department of Pathology and Experimental Therapeutics, University of Barcelona, Carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain; CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), Spain. Electronic address: 8082ifa@gmail.com.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species
keywords: Aging; Lipoxidation; Oligomers; Oxidative damage