The methionine sulfoxide reductases MsrA and MsrB reduce Met(O) to Met in epimer-specific fashion. In Drosophila, the major ecdysone induced protein is MsrA, which is regulated by the EcR-USP complex. We tested Kc cells for induction of MsrA, MsrB, EcR, and CA T by ecdysone and found that MsrA and the EcR were induced by ecdysone, but MsrB and CA T were not. When we tested for resistance to 20 mM H2O2 toxicity, viability of Kc cells was reduced 3-fold. Pretreatment with 0.2 mu M ecdysone for 48 h prior to exposure to H2O2. increased viability to 77% of controls. The EcR-deficient L57-3-11 knockout line was not responsive to ecdysone, and H2O2 resistance of both control and ecdysone-treated L57-3-11 cells was similar to that of the ecdysone-untreated Kc cells. These results show that hormonal regulation of MsrA is implicated in conferring protection against oxidative stress in the Drosophila model. (c) 2007 Elsevier Inc. All rights reserved.