Bcl-x(L) overexpression attenuates glutathione depletion in FL5.12 cells following interleukin-3 withdrawal
Bcl-x(L) overexpression attenuates glutathione depletion in FL5.12 cells following interleukin-3 withdrawal
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DOI：
10.1042/bj3250315
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发表时间：
1997-07-15
影响因子：
4.1
通讯作者：
Kehrer, JP
中科院分区：
文献类型：
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作者：
Bojes, HK;Datta, K;Kehrer, JP
bcl-2相关基因Bcl-x（L）和bax的蛋白产物可抑制或促进细胞凋亡。氧化损伤，包括谷胱甘肽的损失，已牵连在诱导细胞凋亡。在对照、bax和bcl-x（L）转染的FL5.12细胞[一种白细胞介素（IL）-3依赖性鼠幼淋巴细胞系]中评估Eel蛋白影响GSH的能力。在6小时孵育期间，对照和bcl-x（L）转染子中GSH的总体水平大致相同，尽管在重新接种后24小时，bcl-x（L）转染子中的水平增加。过表达bax的细胞中GSH减少了约36%。这些细胞系的超氧化物歧化酶，过氧化氢酶，谷胱甘肽过氧化物酶或谷胱甘肽还原酶的活性之间没有一致的差异。在IL-3撤出后，已知引起这些细胞凋亡的条件下，在对照和bax转染子中发生细胞内GSH的快速损失，这在凋亡开始之前。GSH耗竭不能归因于细胞内氧化，但似乎是由于易位出细胞。过表达bcl-x（L）的细胞在IL-3撤除后没有丢失显著量的GSH，并且没有明显的凋亡。这些结果表明GSH在bcl-x（L）防止细胞死亡的机制中可能起作用。
Bcl-x(L) land 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 Eel proteins to affect GSH was assessed in control, bax- and bcl-x(L)-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-x(L), transfectants during the 6h incubation period, although levels increased in bcl-x(L) transfectants 24h after replating. GSH in cells overexpressing bax was reduced by similar to 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-x(L) 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-x(L) prevents cell death.