Published ahead of print on January 6, 2006, doi:10.1165/rcmb.2005-0333OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0333OC Transgenic Mice Overexpressing Peroxiredoxin 6 Show Increased Resistance to Lung Injury in HyperoxiaInstitute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, and Department of Biology, Fairfield University, Fairfield, Connecticut Correspondence and requests for reprints should be addressed to Aron B. Fisher, M.D., Institute for Environmental Medicine, University of Pennsylvania Medical Center, One John Morgan Building, Philadelphia, PA 19104-6068. E-mail: abf{at}mail.med.upenn.edu
Peroxiredoxin 6 (Prdx6) is a novel peroxidase enzyme that is expressed at a high level in the lung. We tested the hypothesis that transgenic (Tg) mice overexpressing Prdx6 would exhibit increased resistance to hyperoxia-induced lung injury. Wild-type and Tg mice were exposed to 100% O2 and evaluated for survival, lung histopathology, total protein, and nucleated cells in bronchoalveolar lavage fluid (BALF), and oxidation of lung protein and lipids. Prdx6 protein expression and enzyme activity were
Key Words: 1-cys peroxiredoxin • lipid peroxidation • lung inflammation • oxidative stress • protein carbonyls • TBARS This article has been cited by other articles:
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3-fold higher in Tg lungs compared with wild-type. Tg mice survived longer during exposure to 100% O2 (LT50 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 Prdx6 functions as a lung antioxidant enzyme. 
