Cadmium regulates the expression of the CFTR chloride channel in human airway epithelial cells

Jessica Rennolds, Susie Butler, Kevin Maloney, Prosper N. Boyaka, Ian C. Davis, Daren L. Knoell, Narasimham L. Parinandi, Estelle Cormet-Boyaka

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Cadmium is a toxic heavy metal ranked seventh on the Priority List of Hazardous Substances. As a byproduct of smelters, cadmium is a prevalent environmental contaminant. It is also a major component of cigarette smoke, and its inhalation is associated with decreased pulmonary function, lung cancer, and chronic obstructive pulmonary disease. Ion channels, including the cystic fibrosis transmembrane conductance regulator (CFTR), play a central role in maintaining fluid homeostasis and lung functions. CFTR is mostly expressed in epithelial cells, and little is known about the effect of cadmium exposure on lung epithelial cell function. We show that exposure to cadmium decreases the expression of the CFTR protein and subsequent chloride transport in human airway epithelial cells in vitro. Impairment of CFTR protein expression was also observed in vivo in the lung of mice after intranasal instillation of cadmium. We established that the inhibitory effect of cadmium was not a nonspecific effect of heavy metals, as nickel had no effect on CFTR protein levels. Finally, we show that selected antioxidants, including alpha-tocopherol (vitamin E), but not N-acetylcysteine, can prevent the cadmium-induced suppression of CFTR. In summary, we have identified cadmium as a regulator of the CFTR chloride channel present in lung epithelial cells. Future strategies to prevent the deleterious effect of cadmium on epithelial cells and lung functions may benefit from the finding that alpha-tocopherol protects CFTR expression and function.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalToxicological Sciences
Volume116
Issue number1
DOIs
StatePublished - Apr 2 2010

Keywords

  • Airway epithelial cells
  • CFTR
  • Cadmium
  • Vitamin E

ASJC Scopus subject areas

  • Toxicology

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    Rennolds, J., Butler, S., Maloney, K., Boyaka, P. N., Davis, I. C., Knoell, D. L., Parinandi, N. L., & Cormet-Boyaka, E. (2010). Cadmium regulates the expression of the CFTR chloride channel in human airway epithelial cells. Toxicological Sciences, 116(1), 349-358. https://doi.org/10.1093/toxsci/kfq101