Overexpression of the Na-K-ATPase α2-subunit improves lung liquid clearance during ventilation-induced lung injury

Yochai Adir, Lynn C. Welch, Vidas Dumasius, Phillip Factor, Jacob I. Sznajder, Karen M. Ridge

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 α2-subunit contributes to LLC in normal rat lungs. Here we tested whether overexpression of Na-K-ATPase α2-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 α2-subunit gene (Adα2) 7 days before HVT mechanical ventilation. HVT ventilation decreased LLC by ∼50% in untreated, sham, and Adnull-infected rats. Overexpression of Na-K-ATPase α2-subunit prevented the decrease in clearance caused by HVT and was associated with significant increases in Na-K-ATPase α2 protein abundance and activity in peripheral lung basolateral membrane fractions. Ouabain at 10-5 M, a concentration that inhibits the α2 but not the Na-K-ATPase α1, decreased LLC in Adα2-infected rats to the same level as sham and Adnull-infected lungs, suggesting that the increased clearance in Adα2 lungs was due to Na-K-ATPase α2 expression and activity. In summary, we provide evidence that augmentation of the Na-K-ATPase α2-subunit, via gene transfer, may accelerate LLC in the injured lung.

Original languageEnglish (US)
Pages (from-to)L1233-L1237
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 1 2008

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Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Experimental models
  • Gene therapy

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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