Glutathione is a factor of resistance of Jurkat leukemia cells to nitric oxide-mediated apoptosis

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) follow ed by activation of caspases. Here we demonstrate that Jurkat human leukemi a cells which survive alter 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 wh ereas sorted NAO(low) cells died. Moreover, NAO(high) cells acquired an inc reased resistance to the exposure to NO donors which remained unchanged dur ing 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 th e antioxidant glutathione. Depletion of glutathione in these cells with but hionine-sulfoximine (BSO) correlated with a significant stimulation of NO-m ediated apoptosis whereas the exposure of NO-sensitive APO-S cells to the g lutathione precursor N-acetylcysteine (NAC) resulted in a substantial suppr ession of this effect. Our data suggest a complex mechanism of the resisten ce to NO-induced apoptosis in jurkat human leukemia cells in which glutathi one plays an important role. J. Cell. Biochem. 78:578-587, 2000. (C) 2000 W iley-Liss, Inc.