EFFECTS OF N-ACETYL-L-CYSTEINE ON T-CELL APOPTOSIS ARE NOT MEDIATED BY INCREASED CELLULAR GLUTATHIONE

Thiol-containing antioxidants such as N-acetyl-L-cysteine (NAG) are kn own to inhibit apoptosis, although it is unclear whether this effect i s direct or mediated through modulation of intracellular glutathione ( GSH). In the present study, NAC treatment of the murine T-cell hybrido ma DO-11.10 was found to inhibit apoptosis triggered by anti-CD3 antib ody but enhance the process when induced by 6-alpha-methylprednisolone . HPLC measurements showed that these effects were not correlated with the levels of GSH or glutathione disulfide (GSSG) in the cells. Simil ar effects on DNA fragmentation were obtained when the experiments wer e repeated in the presence either of a specific inhibitor of GSH biosy nthesis (buthionine sulfoximine) or the isomer N-acetyl-D-cysteine whi ch cannot be enzymatically converted into GSH. We conclude that NAC ca n have divergent effects on apoptosis independent of changes in either the amount or redox state of intracellular GSH.