title: Oxidant effects on epithelial Na,K-ATPase gene expression and promoter function.
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 alpha-1 and beta-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-receptor constructs transfected into MDCK cells, hyperoxia did not markedly increase transcription of the alpha-1 subunit but doubled transcription of the beta-1 subunit gene. Using 5'-deletion constructs, the region required for the beta-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 beta-1 promoter transcription, likely acting through a novel mechanism.
authors.affiliation: Department of Medicine, University of Minnesota School of Medicine, Minneapolis, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Wendt
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.forename: R
authors.initials: R
authors.lastname: Bair
authors.forename: H
authors.initials: H
authors.lastname: Towle
authors.forename: D H
authors.initials: DH
authors.lastname: Ingbar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D018496:Hyperoxia / Q000201:enzymology / Q000235:genetics; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D016877:Oxidants / Q000633:toxicity*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
chemical_list: D016877:Oxidants; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase