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

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.

• Authors: Jessica Rennolds, Susie Butler, Kevin Maloney, Prosper N Boyaka, Ian C Davis, Daren L Knoell, Narasimham L Parinandi, Estelle Cormet-Boyaka
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 116 Issue 1 Pg. 349-58 (Jul 2010) ISSN: 1096-0929 [Electronic] United States
• PMID: 20363832 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cadmium
• Cystic Fibrosis Transmembrane Conductance Regulator

Topics

• Cadmium (toxicity)
• Cystic Fibrosis Transmembrane Conductance Regulator (metabolism)
• Epithelial Cells (drug effects, metabolism)
• Gene Expression (drug effects)
• Humans
• Polymerase Chain Reaction
• Trachea (cytology, drug effects, metabolism)