Oxygen induction of epithelial Na(+) transport requires heme proteins.
Fetal distal lung epithelial (FDLE) cells exposed to a postnatal O(2) concentration 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 initially cultured in 3% O(2), and then some were switched to a 21% O(2) environment. Incubation of FDLE cells with the iron chelator deferoxamine, CoCl(2), NiCl(2), or an inhibitor of heme synthesis prevented or diminished the O(2) induction of amiloride-sensitive short-circuit current in FDLE cells. Similarly, defer- oxamine and cobalt prevented O(2)-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 O(2) concentration seen at birth requires iron and heme proteins.
Rafii
B
B
Medical Research Council Group in Lung Development, Program in Lung Biology Research, Hospital for Sick Children Research Institute, Ontario, Canada M5G 1X8.
Coutinho
C
C
Otulakowski
G
G
O'Brodovich
H
H
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000502:physiology; D003035:Cobalt / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D053503:Epithelial Sodium Channels; D005333:Fetus / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis; D006420:Hemeproteins / Q000502:physiology*; D007501:Iron / Q000502:physiology; D007502:Iron Chelating Agents / Q000494:pharmacology; D033862:Iron-Binding Proteins; D008168:Lung / Q000166:cytology / Q000196:embryology; D008670:Metals / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D033863:Transferrin-Binding Proteins
D002352:Carrier Proteins; D053503:Epithelial Sodium Channels; D006420:Hemeproteins; D007502:Iron Chelating Agents; D033862:Iron-Binding Proteins; D008670:Metals; D012333:RNA, Messenger; D015222:Sodium Channels; D033863:Transferrin-Binding Proteins; D003035:Cobalt; D006418:Heme; D000584:Amiloride; D012964:Sodium; D007501:Iron; C018021:cobaltous chloride; D010100:Oxygen