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Article
Mice With Targeted Mutation of Peroxiredoxin 6 Develop Normally But Are Susceptible To Oxidative Stress
Journal of Biological Chemistry
  • Xiaosong Wang
  • Shelley A. Phelan, Fairfield University
  • Kristina Forsman-Semb
  • Eric F. Couturier
  • Aaron Brown
  • Charles P. Lerner
  • Beverly Paigen
Document Type
Article
Publication Date
1-1-2003
Disciplines
Abstract
Reactive oxygen species, especially hydrogen peroxide, are important in cellular signal transduction. However, excessive amounts of these species damage tissues and cells by oxidizing virtually all important biomolecules. Peroxiredoxin 6 (PRDX6) (also called antioxidant protein 2, or AOP2) is a novel peroxiredoxin family member whose function in vivo is unknown. Through immunohistochemistry, we have determined that the PRDX6 protein was widely expressed in every tissue examined, most abundantly in epithelial cells. It was found in cytosol, but not in membranes, organelles, and nuclei fractions. Prdx6 mRNA was also expressed in every tissue examined. The widespread expression of Prdx6 suggested that its functions were quite important. To determine these functions, we generated Prdx6-targeted mutant (Prdx6-/-) mice, confirmed the gene disruption by Southern blots, PCR, RT-PCR, Western blots, and immunohistochemistry, and compared the effects of paraquat, hydrogen peroxide, and t-butyl hydroperoxide on Prdx6-/- and wild-type (Prdx6+/+) macrophages, and of paraquat on Prdx6-/- and Prdx6+/+ mice. Prdx6-/- macrophages had higher hydrogen peroxide levels, and lower survival rates; Prdx6-/- mice had significantly lower survival rates, more severe tissue damage, and higher protein oxidation levels. Additionally, there were no differences in the mRNA expression levels of other peroxiredoxins, glutathione peroxidases, catalase, superoxide dismutases, thioredoxins, and glutaredoxins between normal Prdx6-/- and Prdx6+/+ mice and those injected with paraquat. Our study provides in vivo evidence that PRDX6 is a unique non-redundant antioxidant that functions independently of other peroxiredoxins and antioxidant proteins.
Comments

This research was originally published in Journal of Biological Chemisty. Wang X, Phelan SA, Forsman-Semb K, Couturier EF, Brown A, Lerner CP, Paigen, B. Mice With Targeted Mutation of Peroxiredoxin 6 Develop Normally But Are Susceptible To Oxidative Stress. J Biol Chem. 2003. 278(27):25179-25190. © the American Society for Biochemistry and Molecular Biology"

Published Citation
Wang X, Phelan SA, Forsman-Semb K, Couturier EF, Brown A, Lerner CP, Paigen, B. (2003) Mice With Targeted Mutation of Peroxiredoxin 6 Develop Normally But Are Susceptible To Oxidative Stress. Journal of Biological Chemistry, 278(27):25179-25190.
DOI
10.1074/jbc.M302706200
None
Peer Reviewed
Citation Information
Xiaosong Wang, Shelley A. Phelan, Kristina Forsman-Semb, Eric F. Couturier, et al.. "Mice With Targeted Mutation of Peroxiredoxin 6 Develop Normally But Are Susceptible To Oxidative Stress" Journal of Biological Chemistry Vol. 278 Iss. 27 (2003)
Available at: http://works.bepress.com/shelley_phelan/6/