Pulmonary biomarkers based on alterations in protein expression after exposure to arsenic

Robert Clark Lantz, Brandon J. Lynch, Scott A Boitano, Gerald S. Poplin, Sally Littau, George Tsaprailis, Jefferey L Burgess

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Objective: Environmental exposure to arsenic results in multiple adverse effects in the lung. Our objective was to identify potential pulmonary protein biomarkers in the lung-lining fluid of mice chronically exposed to low-dose As and to validate these protein changes in human populations exposed to As. Methods: Mice were administered 10 or 50 ppb As (sodium arsenite) in their drinking water for 4 weeks. Proteins in the lung-lining fluid were identified using two-dimensional gel electrophoresis (n = 3) or multidimensional protein identification technology (MUDPIT) (n = 2) coupled with mass spectrometry. Lung-induced sputum samples were collected from 57 individuals (tap water As ranged from ∼ 5 to 20 ppb). Protein levels in sputum were determined by ELISA, and As species were analyzed in first morning void urine. Results: Proteins in mouse lung-lining fluid whose expression was consistently altered by As included glutathione-S-transferase (GST)-omega-1, contraspin, apolipoprotein A-I and A-IV, enolase-1, peroxiredoxin-6 and receptor for advanced glycation end products (RAGE). Validation of the putative biomarkers was carried out by evaluating As-induced alterations in RAGE in humans. Regression analysis demonstrated a significant negative correlation (p = 0.016) between sputum levels, of RAGE and total urinary inorganic As, similar to results seen in our animal model. Conclusion: Combinations of proteomic analyses of animal models followed by specific analysis of human samples provide an unbiased determination of important, previously unidentified putative biomarkers that may be related to human disease.

Original languageEnglish (US)
Pages (from-to)586-591
Number of pages6
JournalEnvironmental Health Perspectives
Volume115
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

arsenite
Arsenic
Biomarkers
biomarker
arsenic
sodium
Lung
protein
Proteins
Sputum
Linings
Fluids
fluid
Peroxiredoxin VI
Animals
Animal Models
proteomics
exposure
sodium arsenite
Phosphopyruvate Hydratase

Keywords

  • Arsenic
  • Human
  • Lavage
  • Lung
  • Mice
  • Proteomics
  • Sputum

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Pulmonary biomarkers based on alterations in protein expression after exposure to arsenic. / Lantz, Robert Clark; Lynch, Brandon J.; Boitano, Scott A; Poplin, Gerald S.; Littau, Sally; Tsaprailis, George; Burgess, Jefferey L.

In: Environmental Health Perspectives, Vol. 115, No. 4, 04.2007, p. 586-591.

Research output: Contribution to journalArticle

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