Tissue Prx I in the protection against Fe-NTA and the reduction of nitroxyl radicals.
Peroxiredoxin I (Prx I) is a key cytoplasmic peroxidase that reduces intracellular hydroperoxides in concert with thioredoxin. To study the role of tissue Prx I in protection from oxidative stress, we generated Prx I-/- mice by gene trapping. We then evaluated the acute-phase tissue damage caused by ferric-nitrilotriacetate (Fe-NTA). Increases in serum aspartate aminotransferase and alanine aminotransferase levels were significantly greater in Prx I-/- than wild-type mice, 4 and 12 h after the injection of Fe-NTA. Using real-time EPR imaging, we examined the reduction of the stable paramagnetic nitroxyl radical 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl in vivo, and found that the half-life of this spin probe in the liver and kidney was significantly prolonged in the Prx I-/- mice. These results demonstrate that Prx I-/- mice have less reducing activity and are more susceptible to the damage mediated by reactive oxygen species in vivo than wild-type mice.
Uwayama
Junya
J
Biomolecular and Integrated Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Hirayama
Aki
A
Yanagawa
Toru
T
Warabi
Eiji
E
Sugimoto
Rika
R
Itoh
Ken
K
Yamamoto
Masayuki
M
Yoshida
Hiroshi
H
Koyama
Akio
A
Ishii
Tetsuro
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000633:toxicity*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005290:Ferric Compounds; D018398:Homeodomain Proteins; D009589:Nitrogen Oxides; C489936:Prrx1 protein, mouse; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013113:Spin Labels; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C039900:nitroxyl; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate