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Tome ME, Briehl MM: Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis. Cell Death Differ. 2001 Sep;8(9):953-61. Treatment of WEHI7.2 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 WEHI7.2 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, WEHI7.2 cell variants selected for resistance to 50, 100 and 200 microM H (2) O (2) were developed. Resistance to H (2) O (2) is accompanied by increased antioxidant enzyme activity, resistance to other oxidants and a delayed loss of viable cells after dexamethasone treatment. In the 200 microM H (2) O (2)-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. |
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