title: Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: implications in cytotoxicity and amyloid-β peptide aggregation.
abstract: Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties. Since both modifications are increased in Alzheimer's disease (AD) due to amyloid-β peptide (Aβ) accumulation, we have studied their effect on albumin, the most abundant protein in cerebrospinal fluid and blood. Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin. Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. Finally, of particular relevance to AD, these modified albumins were significantly less effective in avoiding Aβ aggregation than native albumin. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD.
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Eva
authors: E
authors: Ramos-Fernández
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Marta
authors: M
authors: Tajes
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Ernest
authors: E
authors: Palomer
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Gerard
authors: G
authors: Ill-Raga
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Mònica
authors: M
authors: Bosch-Morató
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Biuse
authors: B
authors: Guivernau
authors: Group of Cardiovascular Epidemiology and Genetics, Hospital del Mar Research Institute (IMIM), Barcelona, Catalonia, Spain.
authors: Irene
authors: I
authors: Román-Dégano
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Abel
authors: A
authors: Eraso-Pichot
authors: Alzheimer Laboratory, Neurology Department, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
authors: Daniel
authors: D
authors: Alcolea
authors: Alzheimer Laboratory, Neurology Department, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
authors: Juan
authors: J
authors: Fortea
authors: Instituto Grifols, Barcelona, Catalonia, Spain.
authors: Laura
authors: L
authors: Nuñez
authors: Instituto Grifols, Barcelona, Catalonia, Spain.
authors: Antonio
authors: A
authors: Paez
authors: Servei d'Anatomia Patológica, Universitat Autónoma de Barcelona (UAB) Hospital del Mar Research Institute (IMIM), Barcelona, Catalonia, Spain.
authors: Francesc
authors: F
authors: Alameda
authors: Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Catalonia, Spain Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Catalonia, Spain Biomolecular Interactions Team, Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Barcelona, Catalonia, Spain.
authors: Xavier
authors: X
authors: Fernández-Busquets
authors: Alzheimer Laboratory, Neurology Department, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
authors: Alberto
authors: A
authors: Lleó
authors: Group of Cardiovascular Epidemiology and Genetics, Hospital del Mar Research Institute (IMIM), Barcelona, Catalonia, Spain.
authors: Roberto
authors: R
authors: Elosúa
authors: Memory Clinic of Fundació ACE. Institut Catalá de Neurociències Aplicades, Barcelona, Catalonia, Spain Neurology Department, Hospital G. Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.
authors: Mercé
authors: M
authors: Boada
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Miguel A
authors: MA
authors: Valverde
authors: Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Francisco J
authors: FJ
authors: Muñoz
mesh_terms: D000368:Aged; D000418:Albumins / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D066329:Protein Aggregates / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000418:Albumins; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; D014357:Trypsin
keywords: Albumin; Alzheimer's disease; amyloid; glycation; nitrotyrosination; oxidative stress