Tissue Prx I in the protection against Fe-NTA and the reduction of nitroxyl radicals.

Junya Uwayama, Aki Hirayama, Toru Yanagawa, Eiji Warabi, Rika Sugimoto, Ken Itoh, Masayuki Yamamoto, Hiroshi Yoshida, Akio Koyama, Tetsuro Ishii

Index: Biochem. Biophys. Res. Commun. 339(1) , 226-31, (2006)

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Abstract

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.