Bojes H K, Datta K, Xu J, Chin A, Simonian P, Nuñez G, Kehrer J P
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712-1074, USA.
Biochem J. 1997 Jul 15;325 ( Pt 2)(Pt 2):315-9. doi: 10.1042/bj3250315.
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.
Bcl-xL和bax是与bcl-2相关的基因，其蛋白质产物要么抑制要么促进细胞凋亡。包括谷胱甘肽缺失在内的氧化损伤与细胞凋亡的诱导有关。在对照细胞、转染了bax和bcl-xL的FL5.12细胞（一种依赖白细胞介素-3的小鼠原淋巴细胞系）中评估了Bcl蛋白影响谷胱甘肽的能力。在6小时的孵育期内，对照细胞和转染了bcl-xL的细胞中谷胱甘肽的总体水平大致相同，尽管在重新铺板24小时后，转染了bcl-xL的细胞中谷胱甘肽水平有所增加。过表达bax的细胞中的谷胱甘肽减少了约36%。这些细胞系在超氧化物歧化酶、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方面没有一致的差异。在撤除白细胞介素-3后（已知这种情况会导致这些细胞凋亡），对照细胞和转染了bax的细胞中细胞内谷胱甘肽迅速丧失，这发生在细胞凋亡开始之前。谷胱甘肽的消耗不能归因于细胞内氧化，而似乎是由于转运出细胞所致。过表达bcl-xL的细胞在撤除白细胞介素-3后不会大量丧失谷胱甘肽，并且没有明显的细胞凋亡。这些结果表明谷胱甘肽在bcl-xL预防细胞死亡的机制中可能发挥作用。
