TY - JOUR
T1 - Serum proteomics signature of Cystic Fibrosis patients
T2 - A complementary 2-DE and LC-MS/MS approach
AU - Charro, Nuno
AU - Hood, Brian L.
AU - Faria, Daniel
AU - Pacheco, Paula
AU - Azevedo, Pilar
AU - Lopes, Carlos
AU - de Almeida, António Bugalho
AU - Couto, Francisco M.
AU - Conrads, Thomas P.
AU - Penque, Deborah
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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.
AB - 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.
KW - 2DE-MALDI-TOF/TOF MS
KW - Cystic Fibrosis
KW - Label-free proteomics
KW - Serum proteome profiling
KW - Shotgun LC-MS/MS
UR - http://www.scopus.com/inward/record.url?scp=78649872123&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2010.10.001
DO - 10.1016/j.jprot.2010.10.001
M3 - Article
AN - SCOPUS:78649872123
SN - 1874-3919
VL - 74
SP - 110
EP - 126
JO - Journal of Proteomics
JF - Journal of Proteomics
IS - 1
ER -