期刊
JOURNAL OF PROTEOME RESEARCH
卷 13, 期 2, 页码 627-639出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr4007602
关键词
biomarker discovery; bronchoalveolar lavage fluid; chronic obstructive pulmonary disease; peptide extracted ion current
资金
- NIH grants [U54HD071594, DA027528, HL103411]
- Center of Protein Therapeutics Consortium
- AHA award [12SDG9450036]
- NIH grant [HL082561]
- University of Buffalo
Proteomic analysis of bronchoalveolar lavage fluid (BALE) in chronic obstructive pulmonary disease (COPD) patients may provide new biomarkers and deeper understanding of the disease mechanisms but remains challenging. Here we describe an ion-current-based strategy for comparative analysis of BALE proteomes from patients with moderate and stable COPD versus healthy controls. The strategy includes an efficient preparation procedure providing quantitative recovery and a nano-LC/MS analysis with a long, heated column. Under optimized conditions, high efficiency and reproducibility Were achieved for each step, enabling a 20-plex comparison of clinical subjects (n = 10/group). Without depletion/fractionation, a total of 423 unique protein groups were quantified under stringent criteria with at least two quantifiable peptides. Seventy-six proteins were determined as significantly altered in COPD, which represent a diversity of biological processes such as alcohol metabolic process, gluconeogenesis/glycolysis, inflammatory response, proteolysis, and oxidation reduction. Interestingly, altered alcohol metabolism responding to oxidant stress is a novel observation in COPD. The prominently elevated key enzymes involved in alcohol metabolism (e.g., ADH1B, ALDH2, and ALDH3A1) may provide a reasonable explanation for a bewildering observation in COPD patients known for decades: the underestimation of the blood alcohol concentrations through breath tests. These discoveries could provide new insights for identifying novel biomarkers and pathological mediators in clinical studies.
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