Regulation of alveolar epithelial function by hypoxia

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Patients with acute respiratory distress syndrome and high-altitude pulmonary oedema build up excess lung fluid, which leads to alveolar hypoxia. In patients with acute respiratory distress syndrome and hypoxia, there is a decrease in oedema fluid clearance, due in part to the downregulation of plasma membrane sodium-potassium adenosine triphosphatase (Na,K-ATPase). In alveolar epithelial cells, acute hypoxia promotes Na,K-ATPase endocytosis from the plasma membrane to intracellular compartments, resulting in inhibition of Na,K-ATPase activity. Exposure to prolonged hypoxia leads to degradation of plasma membrane Na,K-ATPase. The downregulation of plasma membrane Na,K-ATPase reduces adenosine triphosphate demand, as part of a survival mechanism of cellular adaptation to hypoxia. Hypoxia has also been shown to disassemble and degrade the keratin intermediate filament network, a fundamental component of the cell cytoskeleton, affecting epithelial barrier function. Accordingly, better understanding of the mechanisms regulating cellular adaptation to hypoxia may lead to the development of novel therapeutic strategies for acute respiratory distress syndrome and high-altitude pulmonary oedema patients. Copyright

Original languageEnglish (US)
Pages (from-to)1107-1113
Number of pages7
JournalEuropean Respiratory Journal
Volume31
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Alveolar epithelium
  • Hypoxia
  • Keratin intermediate filament
  • Oedema fluid clearance
  • Reactive oxygen species
  • Sodium-potassium adenosine triphosphatase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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