title: Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody.
abstract: Although human JURKAT T lymphocytes induced to undergo apoptosis with anti-Fas/APO-1 antibody were observed to rapidly lose reduced glutathione (GSH), increased concentrations of oxidized products were not detectable. Unexpectedly, the reduced tripeptide was instead quantitatively recovered in the incubation medium of the cells. As GSH loss was blocked by bromosulfophthalein and dibromosulfophthalein, known inhibitors of hepatocyte GSH transport, a specific export rather than nonspecific leakiness through plasma membranes is proposed to be responsible. Apoptosis was delayed when GSH-diethylesters were used to elevate intracellular GSH, although the high capacity of the activated efflux system quickly negated the benefit of this treatment. Stimulation of GSH efflux provides a novel mechanism whereby Fas/APO-1 ligation can deplete GSH. We speculate that it enhances the oxidative tonus of a responding cell without requiring an increase in the production of reactive oxygen species.
authors.affiliation: Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, S-171 77 Stockholm, Sweden.
authors.forename: D J
authors.initials: DJ
authors.lastname: van den Dobbelsteen
authors.forename: C S
authors.initials: CS
authors.lastname: Nobel
authors.forename: J
authors.initials: J
authors.lastname: Schlegel
authors.forename: I A
authors.initials: IA
authors.lastname: Cotgreave
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
authors.forename: A F
authors.initials: AF
authors.lastname: Slater
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000502:physiology; D005089:Exocytosis; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D011480:Protease Inhibitors; D019014:fas Receptor; C086860:glutathione transporter; D010450:Endopeptidases; D005978:Glutathione