Smoking-associated disordering of the airway basal stem/progenitor cell metabotype

Ruba S. Deeb, Matthew S. Walters, Yael Strulovici-Barel, Qiuying Chen, Steven S. Gross, Ronald Crystal

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The airway epithelium is a complex pseudostratified multicellular layer lining the tracheobronchial tree, functioning as the primary defense against inhaled environmental contaminants. The major cell types of the airway epithelium include basal, intermediate columnar, ciliated, and secretory. Basal cells (BCs) are the proliferating stem/progenitor population that differentiate into the other specialized cell types of the airway epithelium during normal turnover and repair. Given that cigarette smoke delivers thousands of xenobiotics and high levels of reactive molecules to the lung epithelial surface, we hypothesized that cigarette smoke broadly perturbs BC metabolism. To test this hypothesis, primary airway BCs were isolated from healthy nonsmokers (n = 11) and healthy smokers (n = 7) and assessed by global metabolic profiling by liquid chromatography-mass spectrometry. The analysis identified 52 significant metabolites in BCs differentially expressed between smokers and nonsmokers (P < 0.05). These changes included metabolites associated with redox pathways, energy production, and inflammatory processes. Notably, BCs from smokers exhibited altered levels of the key enzyme cofactors/substrates nicotinamide adenine dinucleotide, flavin adenine dinucleotide, acetyl coenzyme A, and membrane phospholipid levels. Consistent with the high burden of oxidants in cigarette smoke, glutathione levels were diminished, whereas 3-nitrotyrosine levels were increased, suggesting that protection of airway epithelial cells against oxidative and nitrosative stress is significantly compromised in smoker BCs. It is likely that this altered metabotype is a reflection of, and likely contributes to, the disordered biology of airway BCs consequent to the stress cigarette smoking puts on the airway epithelium.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume54
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

Fingerprint

Stem cells
Stem Cells
Smoking
Tobacco Products
Smoke
Epithelium
Metabolites
Acetyl Coenzyme A
Flavin-Adenine Dinucleotide
Basal Metabolism
Coenzymes
Liquid chromatography
Xenobiotics
Linings
Oxidants
Metabolism
NAD
Mass spectrometry
Glutathione
Liquid Chromatography

Keywords

  • Airway basal cells
  • Cigarette smoke
  • Metabolic profiling
  • Oxidative stress
  • Progenitor cells

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Smoking-associated disordering of the airway basal stem/progenitor cell metabotype. / Deeb, Ruba S.; Walters, Matthew S.; Strulovici-Barel, Yael; Chen, Qiuying; Gross, Steven S.; Crystal, Ronald.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 54, No. 2, 01.02.2016, p. 231-240.

Research output: Contribution to journalArticle

Deeb, Ruba S. ; Walters, Matthew S. ; Strulovici-Barel, Yael ; Chen, Qiuying ; Gross, Steven S. ; Crystal, Ronald. / Smoking-associated disordering of the airway basal stem/progenitor cell metabotype. In: American Journal of Respiratory Cell and Molecular Biology. 2016 ; Vol. 54, No. 2. pp. 231-240.
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