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Am J Physiol Lung Cell Mol Physiol (April 18, 2008). doi:10.1152/ajplung.00076.2007
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Submitted on February 27, 2007
Accepted on April 9, 2008

Overexpression of the Na,K-ATPase {alpha}2 subunit improves lung liquid clearance during ventilation-induced lung injury

Yochai Adir1, Lynn C Welch2, Vidas Dumasius2, Phillip Factor3, Jacob Iasha Sznajder2, and Karen M. Ridge2*

1 Technion-Israel Institute of Technology, Israel
2 Pulmonary and Critical Care, Northwestern Unversity, Chicago, Illinois, United States
3 Medicine, Columbia University, New York, United States

* To whom correspondence should be addressed. E-mail: kridge{at}northwestern.edu.

Mechanical ventilation with high tidal volumes (HVT) impairs lung liquid clearance (LLC) and downregulates alveolar epithelial Na,K-ATPase. We have previously reported that the Na,K-ATPase {alpha}2 subunit contributes to LLC in normal rat lungs. Here we tested whether overexpression of Na,K-ATPase {alpha}2 subunit in the alveolar epithelium would increase clearance in a HVT model of lung injury. We infected rat lungs with a replication incompetent adenovirus that expresses Na,K-ATPase {alpha}2 subunit gene (Ad{alpha}2) 7 days prior to HVT mechanical ventilation. HVT ventilation decreased LLC by ~50% in untreated, sham and Adnull infected rats. Overexpression of Na,K-ATPase {alpha}2 subunit, prevented the decrease in clearance caused by HVT and was associated with significant increases in Na,K-ATPase {alpha}2 protein abundance and activity in peripheral lung Basolateral membrane fractions. Ouabain at 10-5 M, a concentration that inhibits the {alpha}2 but not the Na,K-ATPase {alpha}1, decreased LLC in Ad{alpha}2 infected rats to the same level as sham and Adnull infected lungs suggesting that the increased clearance in Ad{alpha}2 lungs was due to Na,K-ATPase {alpha}2 expression and activity. In summary, we provide evidence that augmentation of the Na,K-ATPase {alpha}2 subunit, via gene transfer, may accelerate LLC in the injured lung.




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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. N. Z. Yu, Z. P. Traylor, and I. C. Davis
Effect of ventilation pressure on alveolar fluid clearance and {beta}-agonist responses in mice
Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L785 - L793.
[Abstract] [Full Text] [PDF]




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