RAPID AND SPECIFIC EFFLUX OF REDUCED GLUTATHIONE DURING APOPTOSIS INDUCED BY ANTI-FAS AP0-1 ANTIBODY/

Although human JURKAT T lymphocytes induced to undergo apoptosis with anti-Fas/APO-1 antibody were observed to rapidly lose reduced glutathi one (GSH), increased concentrations of oxidized products were not dete ctable, Unexpectedly, the reduced tripeptide was instead quantitativel y recovered in the incubation medium of the cells, As GSH loss was blo cked by bromosulfophthalein and dibromosulfophthalein, known inhibitor s of hepatocyte GSH transport, a specific export rather than nonspecif ic leakiness through plasma membranes is proposed to be responsible, A poptosis was de layed when GSH-diethylesters were used to elevate intr acellular GSH, although the high capacity of the activated efflux syst em quickly negated the benefit of this treatment. Stimulation of GSH e fflux provides a novel mechanism whereby Fas/APO-1 ligation can deplet e GSH. We speculate that it enhances the oxidative tonus of a respondi ng cell without requiring an increase in the production of reactive ox ygen species.