MAMMALIAN PEROXIREDOXIN ISOFORMS CAN REDUCE HYDROGEN-PEROXIDE GENERATED IN RESPONSE TO GROWTH-FACTORS AND TUMOR-NECROSIS-FACTOR-ALPHA

Mammalian tissues express three immunologically distinct peroxiredoxin (Prx) proteins (Prx I, II, and III), which are the products of distin ct genes. With the use of recombinant proteins Prx I, II, and III, all have now been shown to possess peroxidase activity and to rely on Trx as a source of reducing equivalents for the reduction of H2O2. Prx I and II are cytosolic proteins, whereas Prx III is localized in mitocho ndria. Transient overexpression of Prx I or II in cultured cells showe d that they were able to eliminate the intracellular H2O2 generated in response to growth factors. Moreover, the activation of nuclear facto r kappa B (NF kappa B) induced by extracellularly added H2O2 or tumor necrosis factor-alpha was blocked by overproduction of Prx II. These r esults suggest that, together with glutathione peroxidase and catalase , Prx enzymes Likely play an important role in eliminating peroxides g enerated during metabolism. In addition, Prx I and II might participat e in the signaling cascades of growth factors and tumor necrosis facto r-alpha by regulating the intracellular concentration of H2O2.