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• W2073278082 abstract "Murine leukemia L1210 cells grown for 5–7 d in the presence of 1% serum without added selenium [Se(−) cells] expressed < 5% of the glutathione peroxidase (GPX) activity of selenium-supplemented controls [Se(+) cells]. Clonogenic survival assays indicated that t-butyl hydroperoxide (t-BuOOH) is much more toxic to Se(−) cells (LC50 ∼ 10 μM) than to Se(+) or selenium-repleted [Se(−/+)] cells (LC50 ∼ 250 μM). Hypersensitivity of Se(−) cells to t-BuOOH was partially reversed treating them with Ebselen, a selenoperoxidase mimetic; thus, selenoperoxidase insufficiency was probably the most serious defect of Se deprivation. Cytotoxicity of t-BuOOH was inhibited by desferrioxamine and by α-tocopherol, indicating that redox iron and free radical intermediates are involved. Elevated sensitivity of Se(−) cells to t-BuOOH was accompanied by an increased susceptibility to free radical lipid peroxidation, which became even more pronounced in cells that had been grown in arachidonate (20:4, n − 6) supplement media. The glutathione (GSH) is required for cytoprotection was established by showing that Se(+) cells are less resistant to t-BuOOH after exposure to buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. Coupled enzymatic assays indicated the Se(+) or Se(−/+) cells metabolize t-BuOOH 20–50 times more rapidly than Se(−), consistent with the measured difference in GPX activities of these cells. Correspondingly, when challenged the with t-BuOOH, Se(+) cells showed an initial loss of GSH and elevation of GSSG that exceeded that of Se(−) cells. It was further shown that like Se(−) cells, BSO-or BCNU-treated Se(+) cells metabolized t-BuOOH more slowly than nontreated controls. These results clearly indicate that selenoperoxidase action in the glutathione cycle is a vital element in cellular defense against toxic hydroperoxides." @default.
• W2073278082 created "2016-06-24" @default.
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• W2073278082 date "1993-03-01" @default.
• W2073278082 modified "2023-09-23" @default.
• W2073278082 title "Selenoperoxidase-mediated cytoprotection against the damaging effects of tert-butyl hydroperoxide on leukemia cells" @default.
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• W2073278082 doi "https://doi.org/10.1016/0891-5849(93)90022-m" @default.
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