title: Salivary proteome and peptidome profiling in type 1 diabetes mellitus using a quantitative approach.
abstract: In the present study, we applied iTRAQ-based quantitative approach to explore the salivary proteome and peptidome profile in selected subjects with type 1 diabetes, with and without microvascular complications, aiming to identify disease-related markers. From a total of 434 distinct proteins, bactericidal/permeability-increasing protein-like 1 and pancreatic adenocarcinoma up-regulated factor were found in higher levels in the saliva of all patients while increased content of other proteins like alpha-2-macroglobulin, defensin alpha 3 neutrophil-specific, leukocyte elastase inhibitor, matrix metalloproteinase-9, neutrophil elastase, plastin-2, protein S100-A8 and protein S100-A9 were related with microvascular complications as retinopathy and nephropathy. Protein-protein interaction network analysis suggests the functional clusters defense, inflammation and response to wounding as the most significantly associated with type 1 diabetes pathogenesis. Peptidome data not only support a diabetes-related higher susceptibility of salivary proteins to proteolysis (mainly of aPRP, bPRP1 and bPRP2), but also evidenced an increased content of some specific protein fragments known to be related with bacterial attachment and the accumulation of phosphopeptides involved in tooth protection. Overall, the salivary protein and peptide profile highlights the importance of the innate immune system in the pathogenesis of type 1 diabetes mellitus and related complications. This study provides an integrated perspective of salivary proteome and peptidome that should be further explored in future studies targeting specific disease markers.
authors: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro , Portugal.
authors: Armando
authors: A
authors: Caseiro
authors: Rita
authors: R
authors: Ferreira
authors: Ana
authors: A
authors: Padrão
authors: Cláudio
authors: C
authors: Quintaneiro
authors: Amélia
authors: A
authors: Pereira
authors: Rosário
authors: R
authors: Marinheiro
authors: Rui
authors: R
authors: Vitorino
authors: Francisco
authors: F
authors: Amado
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: C578813:A2M protein, human; C466096:BPIFB2 protein, human; D002352:Carrier Proteins; D010455:Peptides; D020543:Proteome; D012471:Salivary Proteins and Peptides; D000511:alpha-Macroglobulins