Peroxiredoxin 1 and its role in cell signaling

Peroxiredoxins (Prdxs) are a family of small (22-27 kDa) non-seleno peroxidases currently known to possess six mammalian isoforms. Although their individual roles in cellular redox regulation and antioxidant protection are quite distinct, they all catalyze peroxide reduction of H2O2, organic hydroperoxides and peroxynitrite.(1,2) They are found to be expressed ubiquitously and in high levels,(3) suggesting that they are both an ancient and important enzyme family. Prdxs can be divided into three major subclasses: typical 2-cysteine (2-Cys) Prdxs (Prdx1-4), atypical 2-Cys Prdx (Prdx 5) and 1-Cys Prdx (Prdx 6). Recent evidence suggests that 2-Cys peroxiredoxins are more than "just simple peroxidases". This hypothesis has been discussed elegantly in recent review articles, considering "over"-oxidation of the protonated thiolate peroxidatic cysteine and post-translational modification of Prdxs as processes initiating a mechanistic switch from peroxidase to chaperon function.(4-6) The process of over-oxidation of the peroxidatic cysteine (C P) occurs during catalysis in the presence of thioredoxin (Trx), thus rendering the sulfenic moiety to sulfinic acid,(7) which can be reduced by sulfiredoxin (Srx).(8,9) However, further oxidation to sulfonic acid is believed to promote Prdx degradation or, as recently shown, the formation of oligomeric peroxidase-inactive chaperones(10) with questionable H2O2-scavenging capacity. In the light of this and given that Prdx1 has recently been shown by us(11) and by others(12-17) to interact directly with signaling molecules, we will explore the possibility that H2O2 regulates signaling in the cell in a temporal and spatial fashion via oxidizing Prdx1. Therefore, this review will focus on H2O2 modulating cell signaling via Prdxs by discussing: (1) the activity of Prdxs towards H2O2; (2) sub cellular localization and availability of other peroxidases, such as catalase or glutathione peroxidases; (3) the availability of Prdxs reducing systems, such as thioredoxin and sulfiredoxin and lastly, (4) Prdx1 interacting signaling molecules.