Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis

Treatment of WEH17.2 cells, a mouse thymoma-derived cell line, with dexamethasone, a synthetic glucocorticoid, causes the cells to undergo apoptosis. Previous work has shown that treatment of WEH17.2 cells with dexamethasone results in a downregulation of antioxidant defense enzymes, suggesting that increased oxidative stress may play a role in glucocorticoid-induced apoptosis. To test whether resistance to oxidative stress causes resistance to dexamethasone-induced apoptosis, WEH17.2 cell variants selected for resistance to 50, 100 and 200 μM H₂O₂ were developed. Resistance to H₂O₂ is accompanied by increased antioxidant enzyme activity, resistance to other oxidants and a delayed loss of viable cells after dexamethasone treatment. In the 200 μM H₂O₂-resistant cell variant the delay in cell loss is correlated with delayed release of cytochrome c from the mitochondria into the cytosol. This suggests that reactive oxygen species play a role in a signaling event during steroid-mediated apoptosis in lymphocytes.