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- W2102688901 abstract "Glutathione depletion either decreased or increased death-receptor–mediated apoptosis in previous studies. Comparison of the durations of glutathione depletion before death-receptor stimulation in these studies might suggest a different effect of prolonged versus acute thiol depletion. We compared the effects of the prolonged glutathione depletion caused by a sulfur amino acid–deficient (SAA−) diet and the acute depletion caused by a single dose of phorone on hepatic apoptosis triggered by the administration of an agonistic anti-Fas antibody. The chronic SAA− diet did not affect hepatic Fas or Bcl-XL, but increased p53 and Bax, and exacerbated Fas-mediated mitochondrial membrane depolarization, electron-microscopy–proven outer mitochondrial membrane rupture, cytochrome c translocation to the cytosol, and caspase 3 activation. These effects were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. The SAA− diet increased internucleosomal DNA fragmentation, the percentage of apoptotic hepatocytes, serum alanine transaminase (ALT) activity, and mortality after Fas stimulation. Despite a similar decrease in hepatic glutathione, administration of a single dose of phorone 1 hour before the anti-Fas antibody did not change p53 or Bax, and did not enhance Fas-induced mitochondrial permeability transition and toxicity. However, 4 repeated doses of phorone (causing more prolonged glutathione depletion) increased Bax and Fas-mediated toxicity. In conclusion, a chronic SAA− diet, but not acute phorone administration, increases p53 and Bax, and enhances Fas-induced mitochondrial permeability transition and apoptosis. Thiol depletion could cause oxidative stress that requires several hours to increase p53; the latter induces Bax, which translocates to mitochondria after Fas stimulation." @default.
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- W2102688901 date "2001-05-01" @default.
- W2102688901 modified "2023-10-15" @default.
- W2102688901 title "Prolonged, but not acute, glutathione depletion promotes Fas-mediated mitochondrial permeability transition and apoptosis in mice" @default.
- W2102688901 doi "https://doi.org/10.1053/jhep.2001.24235" @default.
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