title: Depletion of pulmonary EC-SOD after exposure to hyperoxia.
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.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pennsylvania 15261, USA. tdoury@imap.pitt.edu
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schaefer
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Fattman
authors.forename: Augustine
authors.initials: A
authors.lastname: Choi
authors.forename: Karen E
authors.initials: KE
authors.lastname: Weck
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D018496:Hyperoxia / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology; D011650:Pulmonary Alveoli / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D013482:Superoxide Dismutase