Modulation of rat lung Na+,K(+)-ATPase gene expression by hyperoxia.
Rats exposed to 85% O2 for 5-7 days develop tolerance to otherwise lethal hyperoxia (100% O2). The rate of alveolar fluid clearance increases during adaptation to hyperoxia, due in part to increased alveolar epithelial sodium channel activity. In these studies, we have investigated molecular mechanisms leading to increased lung Na+,K(+)-ATPase activity in hyperoxia. We exposed adult rats to 85% O2 (sublethal hyperoxia) for 7 days, followed by 2, 3, or 4 days in 100% O2. Steady-state levels of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNAs increased in whole lung tissue during hyperoxia exposures. Stability of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNA messages in whole lung RNA did not change significantly. Thus, lung Na+,K(+)-ATPase gene expression in sublethal hyperoxia appears to be regulated in part at the transcriptional level. Alveolar epithelial type II (ATII) cell Na+,K(+)-ATPase alpha 1 and beta 1 subunit proteins, measured by quantitative immunofluorescence, increased significantly after sublethal hyperoxia and 100% O2 exposures. Increases in lung fluid clearance after sublethal hyperoxia are associated with increased ATII cell Na+,K(+)-ATPase protein and whole lung Na+,K(+)-ATPase mRNA expression, which correspond to previously described increases in epithelial sodium channel expression under these conditions.
Johnson
C R
CR
Department of Anesthesiology, University of Alabama at Birmingham 35294-0015, USA.
Guo
Y
Y
Helton
E S
ES
Matalon
S
S
Jackson
R M
RM
D000818:Animals; D004355:Drug Stability; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000201:enzymology* / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D011650:Pulmonary Alveoli / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000096:biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics
D046911:Macromolecular Substances; D012333:RNA, Messenger; D015222:Sodium Channels; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen