Broome H E, Dargan C M, Krajewski S, Reed J C
Department of Pathology, University of California, San Diego; La Jolla 92093-0612, USA.
J Immunol. 1995 Sep 1;155(5):2311-7.
Bcl-2, bcl-x, and bax genes code for proteins that affect the susceptibility of cells to apoptosis. In general, the expression of bcl-2 or bcl-x inhibits apoptosis while bax promotes apoptosis. We examined the levels of these proteins by immunoblotting in resting and activated T cells and in thymocytes. Bcl-2 and Bax proteins vary coordinately, but Bcl-x varies independently: Bcl-2 and Bax are higher in splenic T cells than in thymocytes, and their levels increase even more after T cell activation. In contrast, Bcl-x is almost undetectable in splenic T cells but is manyfold greater in thymocytes and in activated splenic T cells. When CTLL-2 cells or activated T cells are starved of IL (IL-2), the level of Bcl-x but not Bcl-2 protein drops before the onset of apoptosis. Stable transfection of either bcl-2 or bcl-x expression plasmids promotes the survival of CTLL-2 cells in the setting of IL-2 withdrawal. Over 70 to 90% of the transfected cells remain viable at 48 h after IL-2 withdrawal when all of the control transfected cells are apoptotic. These findings suggest that a decrease in Bcl-x protein levels precedes apoptosis after IL-2 withdrawal in T cells and that transfected bcl-2 promotes survival after IL-2 withdrawal by functionally masking this drop in Bcl-x.
Bcl-2、bcl-x和bax基因编码的蛋白质会影响细胞对凋亡的易感性。一般来说，bcl-2或bcl-x的表达会抑制凋亡，而bax则促进凋亡。我们通过免疫印迹法检测了静息和活化的T细胞以及胸腺细胞中这些蛋白质的水平。Bcl-2和Bax蛋白的变化是协同的，但Bcl-x的变化是独立的：脾脏T细胞中的Bcl-2和Bax高于胸腺细胞，并且在T细胞活化后其水平进一步升高。相反，脾脏T细胞中几乎检测不到Bcl-x，但在胸腺细胞和活化的脾脏T细胞中其含量要高很多倍。当CTLL-2细胞或活化的T细胞缺乏白细胞介素（IL-2）时，在凋亡开始前Bcl-x蛋白水平下降，但Bcl-2蛋白水平没有下降。在IL-2撤除的情况下，稳定转染bcl-2或bcl-x表达质粒可促进CTLL-2细胞的存活。当所有对照转染细胞都发生凋亡时，超过70%至90%的转染细胞在撤除IL-2后48小时仍保持存活。这些发现表明，在T细胞撤除IL-2后，Bcl-x蛋白水平的下降先于凋亡，并且转染的bcl-2通过在功能上掩盖Bcl-x的这种下降来促进撤除IL-2后的存活。
