Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis.
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.
Tome
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ME
Department of Pathology, University of Arizona, Tucson, AZ 85724, USA.
Briehl
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MM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D010269:Paraquat / Q000494:pharmacology; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D019284:Thapsigargin; D005047:Etoposide; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D019311:Staurosporine; D010269:Paraquat