Involvement of thio-, peroxi-, and glutaredoxins in cellular redox-dependent processes.
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.
Kalinina
E V
EV
Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, 119991, Russia.
Chernov
N N
NN
Saprin
A N
AN
D000818:Animals; D002477:Cells / Q000378:metabolism*; D054477:Glutaredoxins / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*
D054477:Glutaredoxins; D013879:Thioredoxins; D054464:Peroxiredoxins; D013880:Thioredoxin-Disulfide Reductase