title: Proteomic profiling of human plasma by iTRAQ reveals down-regulation of ITI-HC3 and VDBP by cigarette smoking.
abstract: Biomarkers in noninvasive fluids indicative of cigarette smoke's effects are urgently needed. In this pilot study, we utilized the proteomic approach, isobaric Tags for Relative and Absolute Quantitation (iTRAQ), to identify differentially expressed plasma proteins in healthy cigarette smokers compared to healthy nonsmokers; select proteins were further confirmed by immunoblot analysis. Significant, differentially expressed proteins identified in the plasma separated subjects based on their condition as smokers or nonsmokers. Several of the proteins identified in this study are associated with immunity and inflammatory responses and have been shown to be associated with tobacco-related diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer. Proteins up-regulated in smokers included complement component 8 polypeptide chains α, β, and γ, and mannose-binding protein C, and proteins down-regulated included inter-α-trypsin inhibitor heavy chain H3 (ITI-HC3) and vitamin D-binding protein (VDBP). In addition, gelsolin and vitronectin, known tissue leakage proteins, were up- and down-regulated, respectively. Our results demonstrate for the first time that chronic cigarette smoking can influence the expression profile of the human plasma proteome. Proteins identified in this pilot study may serve as candidate biomarkers of diseases resulting from exposure to cigarette smoke in future molecular epidemiological studies.
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Bortner
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
authors.forename: Arunangshu
authors.initials: A
authors.lastname: Das
authors.forename: Jason
authors.initials: J
authors.lastname: Liao
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.forename: Anne
authors.initials: A
authors.lastname: Stanley
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Stanley
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
mesh_terms: D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D013194:Staining and Labeling / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D014809:Vitamin D-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome; D014809:Vitamin D-Binding Protein; C011877:inter-alpha-inhibitor