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Published ahead of print on January 6, 2006, doi:10.1165/rcmb.2005-0333OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 4, April 2006, 481-486

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Submitted on August 31, 2005
Revised on January 4, 2006

Transgenic Mice Overexpressing Peroxiredoxin 6 Show Increased Resistance to Lung Injury in Hyperoxia

Yan Wang1, Shelley A Phelan2, Yefim Manevich1, Sheldon I Feinstein1, and Aron B Fisher1*

1 Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA, 2 Department of Biology, Fairfield University, Fairfield, CT, USA

* To whom correspondence should be addressed. 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 ~3-fold higher in Tg lungs compared to wild-type. Tg mice survived longer during exposure to 100% O2 (LT50 104±2.8 h in Tg vs. 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 to 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 anti-oxidant enzyme.




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