title: Transgenic mice overexpressing peroxiredoxin 6 show increased resistance to lung injury in hyperoxia.
abstract: Peroxiredoxin 6 (Prd x 6) is a novel peroxidase enzyme that is expressed at a high level in the lung. We tested the hypothesis that transgenic (Tg) mice overexpressing Prd x 6 would exhibit increased resistance to hyperoxia-induced lung injury. Wild-type and Tg mice were exposed to 100% O(2) and evaluated for survival, lung histopathology, total protein, and nucleated cells in bronchoalveolar lavage fluid (BALF), and oxidation of lung protein and lipids. Prd x 6 protein expression and enzyme activity were approximately 3-fold higher in Tg lungs compared with wild-type. Tg mice survived longer during exposure to 100% O(2) (LT(50) 104+/-2.8 h in Tg versus 88.9+/-1.1 h for wild-type). Lung wet/dry weight ratio and total protein and nucleated cell count in lung lavage fluid were significantly greater in wild-type mice at 72 and 96 h of hyperoxia compared with Tg mice. At 96 h of hyperoxia, Tg mice had less epithelial cell necrosis, perivascular edema, and inflammatory cell recruitment by light microscopy, and lower TBARS and protein carbonyls in lung homogenate (P<0.05). These results show that Tg mice have increased defense against lung injury in hyperoxia, providing evidence that Prd x 6 functions as a lung antioxidant enzyme.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania Medical Center, One John Morgan Building, Philadelphia, PA 19104-6068, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Phelan
authors.forename: Yefim
authors.initials: Y
authors.lastname: Manevich
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Feinstein
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010100:Oxygen / Q000502:physiology*; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D050050:Protein Carbonylation; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C515983:Prdx6 protein, mouse; D005978:Glutathione; D010100:Oxygen