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 observedin 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 cadmiuminduced 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.