Posttranslational Nitro-Glycative Modifications of Albumin in Alzheimer's Disease: Implications in Cytotoxicity and Amyloid-beta Peptide Aggregation
Por:
Ramos-Fernandez, E, Tajes, M, Palomer, E, Ill-Raga, G, Bosch-Morato, M, Guivernau, B, Roman-Degano, I, Eraso-Pichot, A, Alcolea, D, Fortea, J, Nunez, L, Paez, A, Alameda, F, Fernandez-Busquets, X, Lleo, A, Elosua, R, Boada, M, Valverde, MA, Munoz, FJ
Publicada:
1 ene 2014
Resumen:
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-beta peptide (A beta) 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 A beta 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.
Filiaciones:
Ramos-Fernandez, E:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Tajes, M:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Palomer, E:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Ill-Raga, G:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Bosch-Morato, M:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Guivernau, B:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Roman-Degano, I:
Hosp del Mar, Res Inst IMIM, Grp Cardiovasc Epidemiol & Genet, Barcelona, Catalonia, Spain
Eraso-Pichot, A:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Alcolea, D:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Hosp Santa Creu & St Pau, Dept Neurol, Alzheimer Lab, Barcelona, Catalonia, Spain
Fortea, J:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Hosp Santa Creu & St Pau, Dept Neurol, Alzheimer Lab, Barcelona, Catalonia, Spain
Nunez, L:
Inst Grifols, Barcelona, Catalonia, Spain
Paez, A:
Inst Grifols, Barcelona, Catalonia, Spain
Alameda, F:
Univ Autonoma Barcelona, Hosp del Mar, Res Inst, Serv Anat Patol, E-08193 Barcelona, Catalonia, Spain
Fernandez-Busquets, X:
Inst Bioengn Catalonia IBEC, Nanomalaria Grp, Barcelona, Catalonia, Spain
Univ Barcelona, Hosp Clin, CRESIB, Barcelona Ctr Int Hlth Res, Barcelona, Catalonia, Spain
Univ Barcelona, Nanosci & Nanotechnol Inst IN2UB, Biomol Interact Team, Barcelona, Catalonia, Spain
Elosua, R:
Hosp del Mar, Res Inst IMIM, Grp Cardiovasc Epidemiol & Genet, Barcelona, Catalonia, Spain
Boada, M:
Memory Clin Fundacio ACE, Inst Catal Neurociencies Aplicades, Barcelona, Catalonia, Spain
Hosp G Univ Vall dHebron, Dept Neurol, Barcelona, Catalonia, Spain
Valverde, MA:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Munoz, FJ:
Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain
Green Accepted
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