Oxidant effects on epithelial Na,K-ATPase gene expression and promoter function

Christine H. Wendt, Renuka Sharma, Robert Bair, Howard Towle, David H. Ingbar

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The lung epithelium resorbs alveolar fluid through combined action of sodium channels and the sodium pump, Na,K-ATPase. The lung often is exposed to hyperoxia in disease states and hyperoxia generates a mixture of reactive oxygen species. In vivo and in vitro exposure of rat lung and alveolar type II cells, respectively, increases gene expression of both the α-1 and β-1 subunits of the sodium pump. In contrast to the primary type II cells, several type II cell lines did not increase sodium pump gene expression with hyperoxia, but the renal tubular epithelial MDCK cell line did. Using promoter-reporter constructs transfected into MDCK cells, hyperoxia did not markedly increase transcription of the α-1 subunit but doubled transcription of the β-1 subunit gene. Using 5'-deletion constructs, the region required for the β-1 increase was localized to a 40-base pair region from -44/-84. The hyperoxic responsiveness of this region was confirmed using constructs with one or two copies of this region placed in minimal promoter-luciferase reporters. This 5' promoter region contains a consensus binding sequence for SP-1, a basal transcription factor but not for binding of other known transcription factors. Thus, hyperoxia induces Na,K-ATPase β-1 promoter transcription, likely acting through a novel mechanism.

Original languageEnglish (US)
Pages (from-to)1213-1217
Number of pages5
JournalEnvironmental health perspectives
Volume106
Issue numberSUPPL. 5
DOIs
StatePublished - 1998

Keywords

  • Alveolar epithelium
  • Ion transport
  • Lung injury
  • MDCK cells
  • Oxidants
  • Sodium pump

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