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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.
AuthorsYan Wang, Shelley A Phelan, Yefim Manevich, Sheldon I Feinstein, Aron B Fisher
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 34 Issue 4 Pg. 481-6 (Apr 2006) ISSN: 1044-1549 [Print] United States
PMID16399955 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Thiobarbituric Acid Reactive Substances
  • Peroxidases
  • Peroxiredoxin VI
  • Peroxiredoxins
  • Prdx6 protein, mouse
  • Glutathione
  • Oxygen
Topics
  • Animals
  • Bronchoalveolar Lavage Fluid (cytology)
  • Enzyme Activation
  • Glutathione (metabolism)
  • Hyperoxia (metabolism, pathology)
  • Lung (metabolism, pathology)
  • Lung Diseases (metabolism, pathology)
  • Male
  • Mice
  • Mice, Transgenic
  • Oxidative Stress
  • Oxygen (physiology)
  • Peroxidases (genetics, metabolism)
  • Peroxiredoxin VI
  • Peroxiredoxins
  • Protein Carbonylation
  • Thiobarbituric Acid Reactive Substances (metabolism)

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