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Originally published In Press as doi:10.1074/jbc.M106846200 on December 10, 2001

J. Biol. Chem., Vol. 277, Issue 7, 5385-5394, February 15, 2002
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Cooperation of Yeast Peroxiredoxins Tsa1p and Tsa2p in the Cellular Defense against Oxidative and Nitrosative Stress*

Chi-Ming Wong, Yuan Zhou, Raymond W. M. Ng, Hsiang-fu Kung, and Dong-Yan JinDagger

From the Institute of Molecular Biology, The University of Hong Kong, Pokfulam Rd., Hong Kong, China

Peroxiredoxins are a family of antioxidant enzymes conserved from bacteria to humans. In Saccharomyces cerevisiae, there exist five peroxiredoxins, among which Tsa2p shares striking homology with the well described Tsa1p but has not been extensively studied. Here we report on the functional characterization of yeast tsa2Delta mutants and the comparison of TSA1 with TSA2. The tsa2Delta and tsa1Delta tsa2Delta cells grew normally under aerobic conditions. However, the tsa1Delta tsa2Delta mutant yeast was more susceptible to oxidants than either tsa1Delta or tsa2Delta cells. Notably, the tsa1Delta tsa2Delta yeast was also hypersensitive to peroxynitrite and sodium nitroprusside. This phenotype was rescued by the expression of either the TSA1 or TSA2 gene. The demonstration of a peroxynitrite reductase activity of Tsa2p in vitro points to a pivotal role for peroxiredoxins in the protection against nitrosative stress. In yeast cells, Tsa1p and Tsa2p exhibited comparable antioxidant activity. While the basal expression level of TSA1 was significantly higher than that of TSA2, the transcription of TSA2 was stimulated more potently by various oxidants. In addition, TSA2 was activated in tsa1Delta cells in a Yap1p-dependent manner. Taken together, our findings implicate the cooperation of Tsa1p and Tsa2p in the cellular defense against reactive oxygen and nitrogen species.

* This work was supported by a grant from the Hong Kong Research Grants Council (Project HKU 7240/00M) (to D.-Y. J.) and a research initiation grant from the Committee on Research and Conference Grants, University of Hong Kong (to D.-Y. J.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Leukemia and Lymphoma Society Scholar. To whom correspondence should be addressed: Dept. of Biochemistry, The University of Hong Kong, 3/F New Medical Complex, Sassoon Rd., Pokfulam, Hong Kong. Tel.: 852-28199245; Fax: 852-28551254; E-mail: dyjin@hkucc.hku.hk.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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