Oxygen induction of epithelial Na+ transport requires heme proteins

Fetal distal lung epithelial (FDLE) cells exposed to a postnatal O-2 concen tration of 21% have higher epithelial Na+ channel (ENaC) mRNA levels and Na + transport relative to FDLE cells grown in a fetal O-2 concentration of 3% . To investigate the mechanism of this process, FDLE monolayers were initia lly cultured in 3% O-2, and then some were switched to a 21% O-2 environmen t. Incubation of FDLE cells with the iron chelator deferoxamine, CoCl2, NiC l2, or an inhibitor of heme synthesis prevented or diminished the O-2 induc tion of amiloride-sensitive short-circuit current in FDLE cells. Similarly, deferoxamine and cobalt prevented O-2-induced ENaC mRNA expression. Exposu re of FDLE cells grown under hypoxic conditions to carbon monoxide increase d both ENaC mRNA expression and amiloride-sensitive short-circuit current. We therefore concluded that induction of ENaC mRNA expression and amiloride -sensitive Na+ transport in FDLE cells by a physiological increase in O-2 c oncentration seen at birth requires iron and heme proteins.