title: 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.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rennolds
authors.forename: Susie
authors.initials: S
authors.lastname: Butler
authors.forename: Kevin
authors.initials: K
authors.lastname: Maloney
authors.forename: Prosper N
authors.initials: PN
authors.lastname: Boyaka
authors.forename: Ian C
authors.initials: IC
authors.lastname: Davis
authors.forename: Daren L
authors.initials: DL
authors.lastname: Knoell
authors.forename: Narasimham L
authors.initials: NL
authors.lastname: Parinandi
authors.forename: Estelle
authors.initials: E
authors.lastname: Cormet-Boyaka
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016133:Polymerase Chain Reaction; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002104:Cadmium; D019005:Cystic Fibrosis Transmembrane Conductance Regulator