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Am J Physiol Lung Cell Mol Physiol 278: L399-L406, 2000;
1040-0605/00 $5.00
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Vol. 278, Issue 2, L399-L406, February 2000

Oxygen induction of epithelial Na+ transport requires heme proteins

Bijan Rafii1, Chris Coutinho1, Gail Otulakowski1, and Hugh O'Brodovich1,2

1 Medical Research Council Group in Lung Development, Program in Lung Biology Research, Hospital for Sick Children Research Institute, and 2 Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada M5G 1X8

Fetal distal lung epithelial (FDLE) cells exposed to a postnatal O2 concentration of 21% have higher epithelial Na+ channel (ENaC) mRNA levels and Na+ transport relative to FDLE cells grown in a fetal O2 concentration of 3%. To investigate the mechanism of this process, FDLE monolayers were initially cultured in 3% O2, and then some were switched to a 21% O2 environment. Incubation of FDLE cells with the iron chelator deferoxamine, CoCl2, NiCl2, or an inhibitor of heme synthesis prevented or diminished the O2 induction of amiloride-sensitive short-circuit current in FDLE cells. Similarly, defer- oxamine and cobalt prevented O2-induced ENaC mRNA expression. Exposure of FDLE cells grown under hypoxic conditions to carbon monoxide increased 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 O2 concentration seen at birth requires iron and heme proteins.

epithelial sodium channel; alveolar epithelium


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