title: Glutathione is a factor of resistance of Jurkat leukemia cells to nitric oxide-mediated apoptosis.
abstract: We have previously reported that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through mitochondrial damage (including degradation of cardiolipin, a major mitochondrial lipid) followed by activation of caspases. Here we demonstrate that Jurkat human leukemia cells which survive after 24 h treatment with NO form subpopulations with higher and lower cardiolipin content (designated as NAO(high) and NAO(low), respectively). Sorted NAO(high) cells were found to survive in culture whereas sorted NAO(low) cells died. Moreover, NAO(high) cells acquired an increased resistance to the exposure to NO donors which remained unchanged during long-term culture. These cells showed a similar cardiolipin content and expressed the same level of anti-apoptotic proteins Bcl-2 and Bcl-x(L) as APO-S unsorted cells but contained significantly higher concentration of the antioxidant glutathione. Depletion of glutathione in these cells with buthionine-sulfoximine (BSO) correlated with a significant stimulation of NO-mediated apoptosis whereas the exposure of NO-sensitive APO-S cells to the glutathione precursor N-acetylcysteine (NAC) resulted in a substantial suppression of this effect. Our data suggest a complex mechanism of the resistence to NO-induced apoptosis in Jurkat human leukemia cells in which glutathione plays an important role.
authors.affiliation: Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, D-69120 Heidelberg, Germany. V.Umansky@dkfz-heidelberg.de
authors.forename: V
authors.initials: V
authors.lastname: Umansky
authors.forename: M
authors.initials: M
authors.lastname: Rocha
authors.forename: R
authors.initials: R
authors.lastname: Breitkreutz
authors.forename: S
authors.initials: S
authors.lastname: Hehner
authors.forename: M
authors.initials: M
authors.lastname: Bucur
authors.forename: N
authors.initials: N
authors.lastname: Erbe
authors.forename: W
authors.initials: W
authors.lastname: Dröge
authors.forename: A
authors.initials: A
authors.lastname: Ushmorov
mesh_terms: D000165:Acridine Orange / Q000378:metabolism; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002308:Cardiolipins / Q000096:biosynthesis / Q000378:metabolism; D002469:Cell Separation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051020:bcl-X Protein
chemical_list: D017304:Annexin A5; C494811:BCL2L1 protein, human; D002308:Cardiolipins; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D019881:Aminoacyltransferases; C093784:glutathione gamma-glutamylcysteinyltransferase; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D005721:Glutamate-Cysteine Ligase; D000165:Acridine Orange; D005978:Glutathione; D016650:Fluorescein-5-isothiocyanate