Adenovirus-mediated transfer of an Na+/K+-ATPase β1 subunit gene improves alveolar fluid clearance and survival in hyperoxic rats

P. Factor*, V. Dumasius, F. Saldias, L. A.S. Brown, J. I. Sznajder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Pulmonary edema is cleared via active Na+ transport by alveolar epithelial Na+/K+-ATPases and Na+ channels. Rats exposed to acute hyperoxia have a high mortality rate, decreased Na+/K+-ATPase function, and decreased alveolar fluid clearance (AFC). We hypothesized that Na+/K+-ATPase subunit gene overexpression could improve AFC in rats exposed to hyperoxia. We delivered 4 x 109 PFU of recombinant adenoviruses containing rat α1 and β1 Na+/K+-ATPase subunit cDNAs (adα1 and adβ1, respectively) to rat lungs 7 days prior to exposure to 100% O2 for 64 hr. As compared with controls and adα1, AFC in the adβ1 rats was increased by >300%. Permeability for large solutes was less in the adβ1 than in the other hyperoxia groups. Glutathione oxidation, but not superoxide dismutase activity, was increased only in the adβ1 group. Survival through 14 days of hyperoxia was 100% in the adβ1 group but was not different from hyperoxic controls in animals given adα1. Our data show that overexpression of a β1 Na+/K+-ATPase subunit augments AFC and improves survival in this model of acute lung injury via antioxidant-independent mechanisms. Conceivably, restoration of AFC via gene transfer of Na+/K+-ATPase subunit genes may prove useful for the treatment of acute lung injury and pulmonary edema.

Original languageEnglish (US)
Pages (from-to)2231-2242
Number of pages12
JournalHuman Gene Therapy
Volume11
Issue number16
DOIs
StatePublished - Nov 1 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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