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

被引：42

作者：

Ramos-Fernandez, Eva ^{[1
]}

Tajes, Marta ^{[1
]}

Palomer, Ernest ^{[1
]}

Ill-Raga, Gerard ^{[1
]}

Bosch-Morato, Monica ^{[1
]}

Guivernau, Biuse ^{[1
]}

Roman-Degano, Irene ^{[2
]}

Eraso-Pichot, Abel ^{[1
]}

Alcolea, Daniel ^{[3
]}

Fortea, Juan ^{[3
]}

Nunez, Laura ^{[4
]}

Paez, Antonio ^{[4
]}

Alameda, Francesc ^{[5
]}

Fernandez-Busquets, Xavier ^{[6
,7
,8
]}

Lleo, Alberto

Elosua, Roberto ^{[2
]}

Boada, Merce ^{[9
,10
]}

Valverde, Miguel A. ^{[1
]}

Munoz, Francisco J. ^{[1
]}

机构：

[1] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopaties, Barcelona, Catalonia, Spain

[2] Hosp del Mar, Res Inst IMIM, Grp Cardiovasc Epidemiol & Genet, Barcelona, Catalonia, Spain

[3] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Hosp Santa Creu & St Pau, Dept Neurol, Alzheimer Lab, Barcelona, Catalonia, Spain

[4] Inst Grifols, Barcelona, Catalonia, Spain

[5] Univ Autonoma Barcelona, Hosp del Mar, Res Inst, Serv Anat Patol, E-08193 Barcelona, Catalonia, Spain

[6] Inst Bioengn Catalonia IBEC, Nanomalaria Grp, Barcelona, Catalonia, Spain

[7] Univ Barcelona, Hosp Clin, CRESIB, Barcelona Ctr Int Hlth Res, Barcelona, Catalonia, Spain

[8] Univ Barcelona, Nanosci & Nanotechnol Inst IN2UB, Biomol Interact Team, Barcelona, Catalonia, Spain

[9] Memory Clin Fundacio ACE, Inst Catal Neurociencies Aplicades, Barcelona, Catalonia, Spain

[10] Hosp G Univ Vall dHebron, Dept Neurol, Barcelona, Catalonia, Spain

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2014年 / 40卷 / 03期

关键词：

Albumin; Alzheimer's disease; amyloid; glycation; nitrotyrosination; oxidative stress; HUMAN-SERUM-ALBUMIN; CENTRAL-NERVOUS-SYSTEM; A-BETA; PROTEIN NITROTYROSINATION; PROTEOMIC IDENTIFICATION; OXIDATIVE STRESS; BRAIN; METHYLGLYOXAL; GLUCOSE; OXIDE;

D O I：

10.3233/JAD-130914

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：643 / 657

页数：15

共 58 条

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