Serum proteomics signature of cystic fibrosis patients: a complementary 2-DE and LC-MS/MS approach.
J Proteomics
; 74(1): 110-26, 2011 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-20950718
ABSTRACT
Complementary 2D-PAGE and 'shotgun' LC-MS/MS approaches were combined to identify medium and low-abundant proteins in sera of Cystic Fibrosis (CF) patients (mild or severe pulmonary disease) in comparison with healthy CF-carrier and non-CF carrier individuals aiming to gain deeper insights into the pathogenesis of this multifactorial genetic disease. 78 differentially expressed spots were identified from 2D-PAGE proteome profiling yielding 28 identifications and postulating the existence of post-translation modifications (PTM). The 'shotgun' approach highlighted altered levels of proteins actively involved in CF abnormal tissue/airway remodeling, protease/antiprotease imbalance, innate immune dysfunction, chronic inflammation, nutritional imbalance and Pseudomonas aeruginosa colonization. Members of the apolipoproteins family (VDBP, ApoA-I, and ApoB) presented gradually lower expression from non-CF to CF-carrier individuals and from those to CF patients, results validated by an independent assay. The multifunctional enzyme NDKB was identified only in the CF group and independently validated by WB. Its functions account for ion sensor in epithelial cells, pancreatic secretion, neutrophil-mediated inflammation and energy production, highlighting its physiological significance in the context of CF. Complementary proteomics-based approaches are reliable tools to reveal pathways and circulating proteins actively involved in a heterogeneous disease such as CF.
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Base de dados:
MEDLINE
Assunto principal:
Eletroforese em Gel Bidimensional
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Cromatografia Líquida
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Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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Proteoma
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Fibrose Cística
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Proteômica
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article