FXYD1 negatively regulates Na(+)/K(+)-ATPase activity in lung alveolar epithelial cells.

Abstract

Acute respiratory distress syndrome (ARDS) is clinical syndrome characterized by decreased lung fluid reabsorption, causing alveolar edema. Defective alveolar ion transport undertaken in part by the Na(+)/K(+)-ATPase underlies this compromised fluid balance, although the molecular mechanisms at play are not understood. We describe here increased expression of FXYD1, FXYD3 and FXYD5, three regulatory subunits of the Na(+)/K(+)-ATPase, in the lungs of ARDS patients. Transforming growth factor (TGF)-β, a pathogenic mediator of ARDS, drove increased FXYD1 expression in A549 human lung alveolar epithelial cells, suggesting that pathogenic TGF-β signaling altered Na(+)/K(+)-ATPase activity in affected lungs. Lentivirus-mediated delivery of FXYD1 and FXYD3 allowed for overexpression of both regulatory subunits in polarized H441 cell monolayers on an air/liquid interface. FXYD1 but not FXYD3 overexpression inhibited amphotericin B-sensitive equivalent short-circuit current in Ussing chamber studies. Thus, we speculate that FXYD1 overexpression in ARDS patient lungs may limit Na(+)/K(+)-ATPase activity, and contribute to edema persistence.

• Authors: Łukasz A Wujak, Anna Blume, Emel Baloğlu, Małgorzata Wygrecka, Jegor Wygowski, Susanne Herold, Konstantin Mayer, István Vadász, Petra Besuch, Heimo Mairbäurl, Werner Seeger, Rory E Morty
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 220 Pg. 54-61 (Jan 2016) ISSN: 1878-1519 [Electronic] Netherlands
• PMID: 26410457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• FXYD3 protein, human
• FXYD5 protein, human
• Ion Channels
• Membrane Glycoproteins
• Membrane Proteins
• Microfilament Proteins
• Neoplasm Proteins
• Phosphoproteins
• phospholemman
• Sodium
• Sodium-Potassium-Exchanging ATPase

Topics

• Adult
• Aged
• Animals
• Cell Line, Tumor
• Epithelial Cells (metabolism)
• Female
• Genetic Vectors
• Humans
• Ion Channels
• Lentivirus (genetics)
• Lung (metabolism)
• Male
• Membrane Glycoproteins (metabolism)
• Membrane Proteins (genetics, metabolism)
• Mice
• Microfilament Proteins
• Middle Aged
• Neoplasm Proteins (genetics, metabolism)
• Phosphoproteins (genetics, metabolism)
• Promoter Regions, Genetic
• Respiratory Distress Syndrome (metabolism)
• Sodium (metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)