Upregulation of rat lung Na-K-ATPase during hyperoxic injury.
A major function of the alveolar epithelium is to keep the airspace free of fluid and preserve gas exchange. Since Na-K-ATPase is believed to be important in this process, we hypothesized that Na-K-ATPase in the rat lung would increase in response to acute lung injury with pulmonary edema. Na-K-ATPase localization, mRNA expression, and protein levels were determined in hyperoxic lung injury. Adult male rats were exposed to greater than 97% oxygen for 60 h followed by recovery in room air. At 60 h of hyperoxia, the wet-to-dry lung weights increased, consistent with edema. Within the alveolar capillary region, the sodium pump remained localized to the type II cell basolateral membrane by immunocytochemistry. By Northern blot analysis, the level of total lung mRNA expression of the alpha 1- and beta-subunits of Na-K-ATPase increased three- to fourfold during hyperoxia compared with unexposed rats. Total lung Na-K-ATPase membrane protein, visualized with a Western blot technique, appeared to increase by 24 h of hyperoxic insult when compared with levels in unexposed animals. The increase in sodium pump gene expression that occurs during hyperoxic insult, followed by an increase in sodium pump membrane protein, suggests that type II cells increase their Na-K-ATPase synthesis as an early response to pulmonary edema and/or hyperoxia.
Nici
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Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Dowin
R
R
Gilmore-Hebert
M
M
Jamieson
J D
JD
Ingbar
D H
DH
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D008565:Membrane Proteins; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen