Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin and their role in signal transduction

A peroxidase from yeast that reduces HA with the use of electrons provided by thioredûxin (Trx) together with homologs from a wide variety of species constitute the peroxiredoxin (Prx) family of proteins.Twelve mammalian Prx members have now been divided into three distinct types, Prx I, II, and III, on the basis of their deduced amino acid sequences and immunological reactivity. With the use of recombinant proteins, Prx I, II, and III have now been shown to possess peroxidase activity and to rely on Trx as a source of reducing equivalents. None of the three proteins exhibited peroxidase activity in the presence of glutaredoxin. All three enzymes showed similar kinetic properties. Immunoblot analysis of various rat tissues and cultured cells indicated that most cell types contain the three Prx isoforms. the sum of which amounts to - 1 to 10 ug per milligram of soluble protein. Prx I and II are cytosolic proteins, whereas Prx III is localized in mitochondria. Transient overexpression of Prx I or II in cultured cells showed that they were able to eliminate the intracellular H ₂₂O ₂generated in response to growth factors. These results suggest that, together with glutathione peroxidase and catalase, Prx enzymes likely play an important role in eliminating peroxides generated during metabolism. In addition, Prx I and II might participate in the signaling cascades of various receptors by regulating the intracellular concentration of HA.