Fig. 1.

Multiple roles of Prx1 in suppression of oxidative stress-induced apoptosis. In addition to the Trx peroxidase activity to eliminate H₂O₂, Prx1 cooperates with Trx in suppression of H₂O₂-induced activation of the two apoptosis signal regulators, ASK1⁽²⁶⁾ and p66^Shc,⁽²⁷⁾ through direct interactions. The activation of ASK1 by oxidant stress is inhibited by reduced form of Trx under low stress conditions. When human embryonic kidney 293 cells were treated with 5 mM H₂O₂ for 20 min, oxidized Trx was replaced by oxidized Prx1 to further suppress ASK1 activation.⁽²⁶⁾ Under low stress conditions, Trx and Prx1 maintain p66^Shc inactive, by keeping it reduced and dimeric form. Under high stress conditions (1.47 mM H₂O₂), Prx1 is oxidized forming a decameric chaperone and separated from p66^Shc, which is phosphorylated at Ser-36. JNK phosphorylates p66^Shc at Ser-36,^(38,39) inducing tetramer formation and translocation of p66^Shc to mitochondria to generate ROS.^(27,37) On the other hand, ionizing radiation activates tyrosine kinase c-Abl⁽⁴¹⁾ and JNK.⁽²⁸⁾ We speculate Prx1 may inhibit activation of c-Abl following ioning radiation. Prx1 indirectly binds JNK through GSTpi, which suppress activation of JNK.⁽²⁸⁾ Prx2 like Prx1 suppresses ASK1 activation in neuronal cells in which Prx2 is highly expressed.⁽²⁹⁾