Adenovirus-mediated transfer of the 1-cys peroxiredoxin gene to mouse lung protects against hyperoxic injury.
1-Cys peroxiredoxin (1-cysPrx) is a novel antioxidant enzyme that has been shown to reduce a broad spectrum of peroxides including phospholipid hydroperoxides. We tested the hypothesis that adenovirus-mediated transfer of the 1-cysPrx gene can protect lungs of mice from oxidant injury. Mice infected with AdLacZ/AdNull were used as a control (AdCon). X-galactosidase staining revealed widespread expression of the LacZ gene in airways and lung alveoli. Compared with AdCon, 1-cysPrx expression was increased about twofold at 3 days after adenovirus infection. Mice with increased Prx expression showed less loss of body weight and longer survival during exposure to 100% O(2) or to 85% O(2) for 4 days followed by 100% O(2). At 72 h of 100% O(2) exposure, AdPrx infection protected mouse lungs from injury as indicated by less pleural effusion, lower lung wet/dry weight, less protein and fewer nucleated cells in bronchoalveolar lavage fluid, and lower content of thiobarbituric acid-reactive substances and protein carbonyls in lung homogenate. These findings show that increased expression of 1-cysPrx through adenovirus-mediated gene transfer protects mouse lungs from hyperoxic injury and delays death.
Wang
Yan
Y
Institute for Environmental Medicine, University of Pennsylvania Medical Center, 1 John Morgan Bldg., Philadelphia, PA 19104-6068, USA.
Manevich
Yefim
Y
Feinstein
Sheldon I
SI
Fisher
Aron B
AB
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D018496:Hyperoxia / Q000378:metabolism* / Q000401:mortality / Q000628:therapy*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics*; D054464:Peroxiredoxins; D010996:Pleural Effusion / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D010544:Peroxidases; D054464:Peroxiredoxins