Modulation of Rat Lung Na+,K+-Atpase Gene Expression by Hyperoxia

Abstract

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 α1 and β1 subunit mRNAs increased in whole lung tissue during hyperoxia exposures. Stability of the Na+,K+-ATPase α1 and β1 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 α1 and β1 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+-ATPaseprotein and whole lung Na+,K+-ATPase mRNA expression, which correspond to previously described increases in epithelial sodium channel expression under these conditions.