REVIEW: Involvement of Thio-, Peroxi-, and Glutaredoxins in Cellular Redox-Dependent Processes

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E. V. Kalinina^1,2, N. N. Chernov³, and A. N. Saprin^1*

¹Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, ul. Kosygina 4, 119991 Moscow, Russia; fax: (495) 938-2533; E-mail: kevsan@orc.ru

²Institute of Cytochemistry and Molecular Pharmacology, 6-ya Radial'naya ul. 24/14, 115404 Moscow, Russia

³Peoples' Friendship University of Russia, ul. Miklukho-Maklaya 8, 117198 Moscow, Russia

^* To whom correspondence should be addressed.

Received November 7, 2007; Revision received July 24, 2008

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Among the key antioxidant enzymes, thioredoxin and glutaredoxin systems play an important role in cell defense against oxidative stress and maintenance of redox homeostasis owing to the regulation of thiol-disulfide exchange. The thioredoxin isoforms Trx1 (cytoplasmic form) and Trx2 (mitochondrial form) can reduce inter- and intramolecular disulfide bonds in proteins, in particular, in oxidized peroxiredoxins, which disrupt organic hydroperoxides, H₂O₂, and peroxynitrite. NADPH-dependent thioredoxin reductase, which reduces a broad range of substrates including oxidized form of thioredoxin, can also directly reduce lipid hydroperoxides, H₂O₂, and dehydroascorbic and lipoic acids. Glutaredoxin, whose major isoforms in mammals are Grx1, Grx2, and Grx5, as well as thioredoxin, catalyzes S-glutathionylation and deglutathionylation of proteins to protect SH-groups from oxidation and restore functionally active thiols. However, in contrast to thioredoxin, glutaredoxin reduces GSH-mixed disulfides and catalyzes the reaction not only via a dithiol mechanism but also via monothiol reduction. In addition to the role in cellular antioxidant defense, all of the reviewed redox proteins (thioredoxin, thioredoxin reductase, peroxiredoxin, and glutaredoxin) have a number of significant functions required for cell viability: they regulate transcription factor activities, play the role of growth factors, serve as enzyme cofactors, take part in regulation of cell cycle, and are involved in antiapoptotic mechanisms.

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KEY WORDS: oxidative stress, thioredoxin, thioredoxin reductase, peroxiredoxin, glutaredoxin, redox-dependent processes

DOI: 10.1134/S0006297908130099

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