Bcl-xL overexpression attenuates glutathione depletion in FL5.12 cells following interleukin-3 withdrawal.
Bcl-xL and bax are bcl-2-related genes whose protein products either inhibit or promote apoptosis. Oxidative damage, including the loss of glutathione, has been implicated in the induction of apoptosis. The ability of the Bcl proteins to affect GSH was assessed in control, bax- and bcl-xL-transfected FL5.12 cells [an interleukin (IL)-3-dependent murine prolymphocytic cell line]. Overall levels of GSH were approximately the same in control and bcl-xL transfectants during the 6 h incubation period, although levels increased in bcl-xL transfectants 24 h after replating. GSH in cells overexpressing bax was reduced by approximately 36%. There were no consistent differences between these cell lines in the activities of superoxide dismutase, catalase, glutathione peroxidase or glutathione reductase. Following IL-3 withdrawal, a condition known to cause apoptosis in these cells, a rapid loss of intracellular GSH occurred in control and bax transfectants, which preceded the onset of apoptosis. GSH depletion could not be attributed to intracellular oxidation but rather seemed to occur due to a translocation out of the cell. Cells overexpressing bcl-xL did not lose significant amounts of GSH upon withdrawal of IL-3, and no apoptosis was evident. These results suggest a possible role for GSH in the mechanism by which bcl-xL prevents cell death.
Bojes
H K
HK
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712-1074, USA.
Datta
K
K
Xu
J
J
Chin
A
A
Simonian
P
P
Nuñez
G
G
Kehrer
J P
JP
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000975:Antioxidants; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione