Depletion of pulmonary EC-SOD after exposure to hyperoxia

Tim D. Oury, Lisa M. Schaefer, Cheryl L. Fattman, Augustine Choi, Karen E. Weck, Simon C. Watkins

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Extracellular superoxide dismutase (EC-SOD) is highly expressed in lung tissue. EC-SOD contains a heparin-binding domain that is sensitive to proteolysis. This heparin-binding domain is important in allowing EC-SOD to exist in relatively high concentrations in specific regions of the extracellular matrix and on cell surfaces. EC-SOD has been shown to protect the lung against hyperoxia in transgenic and knockout studies. This study tests the hypothesis that proteolytic clearance of EC-SOD from the lung during hyperoxia contributes to the oxidant-antioxidant imbalance that is associated with this injury. Exposure to 100% oxygen for 72 h resulted in a significant decrease in EC-SOD levels in the lungs and bronchoalveolar lavage fluid of mice. This correlated with a significant depletion of EC-SOD from the alveolar parenchyma as determined by immunofluorescence and immunohistochemistry. EC-SOD mRNA was unaffected by hyperoxia; however, there was an increase in the ratio of proteolyzed to uncut EC-SOD after hyperoxia, which suggests that hyperoxia depletes EC-SOD from the alveolar parenchyma by cutting the heparin-binding domain. This may enhance hyperoxic pulmonary injury by altering the oxidant-antioxidant balance in alveolar spaces.

Original languageEnglish (US)
Pages (from-to)L777-L784
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number4 27-4
DOIs
StatePublished - Oct 2002

Keywords

  • Acute lung injury
  • Adult respiratory distress syndrome
  • Antioxidants
  • Extracellular superoxide dismutase
  • Oxidative stress
  • Proteolysis

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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