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

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

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. © 2014 IOS Press and the authors. All rights reserved.
Original languageEnglish
Pages (from-to)643-657
JournalJournal of Alzheimer's Disease
Volume40
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Albumin
  • Alzheimer's disease
  • amyloid
  • glycation
  • nitrotyrosination
  • oxidative stress

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