Posttranslational Nitro-Glycative Modifications of Albumin in Alzheimer’s Disease: Implications in Cytotoxicity and Amyloid-β Peptide Aggregation

Eva Ramos-Fernández, Marta Tajes, Ernest Palomer, Gerard ILL-Raga, Mònica Bosch-Morató, Biuse Guivernau, Irene Román-Dégano, Abel Eraso-Pichot, Daniel Alcolea, Juan Fortea, Laura Nuñez, Antonio Paez, Francesc Alameda, Xavier Fernández-Busquets, Alberto Lleó, Roberto Elosúa, Mercé Boada, Miguel A. Valverde, Francisco J. Muñoz
JAD. 2014-04-23; 40(3): 643-657
DOI: 10.3233/JAD-130914

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1. J Alzheimers Dis. 2014;40(3):643-57. doi: 10.3233/JAD-130914.

Posttranslational nitro-glycative modifications of albumin in Alzheimer’s
disease: implications in cytotoxicity and amyloid-β peptide aggregation.

Ramos-Fernández E(1), Tajes M(1), Palomer E(1), Ill-Raga G(1), Bosch-Morató M(1),
Guivernau B(1), Román-Dégano I(2), Eraso-Pichot A(1), Alcolea D(3), Fortea J(3),
Nuñez L(4), Paez A(4), Alameda F(5), Fernández-Busquets X(6), Lleó A(3), Elosúa
R(2), Boada M(7), Valverde MA(1), Muñoz FJ(1).

Author information:
(1)Laboratory of Molecular Physiology and Channelopaties, Department of
Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona,
Catalonia, Spain.
(2)Group of Cardiovascular Epidemiology and Genetics, Hospital del Mar Research
Institute (IMIM), Barcelona, Catalonia, Spain.
(3)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.
(4)Instituto Grifols, Barcelona, Catalonia, Spain.
(5)Servei d’Anatomia Patológica, Universitat Autónoma de Barcelona (UAB) Hospital
del Mar Research Institute (IMIM), Barcelona, Catalonia, Spain.
(6)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.
(7)Memory Clinic of Fundació ACE. Institut Catalá de Neurociències Aplicades,
Barcelona, Catalonia, Spain Neurology Department, Hospital G. Universitari Vall
d’Hebron, Barcelona, Catalonia, Spain.

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.

DOI: 10.3233/JAD-130914
PMID: 24503620 [Indexed for MEDLINE]

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