Rathmell J C, Vander Heiden M G, Harris M H, Frauwirth K A, Thompson C B
Department of Cancer Biology and Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia 19104, USA.
Mol Cell. 2000 Sep;6(3):683-92. doi: 10.1016/s1097-2765(00)00066-6.
Without receptor stimulation, cells from multicellular organisms die by apoptosis. Here we show that lymphocytes deprived of receptor stimulation undergo progressive atrophy before commitment to apoptosis. Following loss of receptor engagement, lymphocytes rapidly downregulated the glucose transporter, glut1. This was accompanied by reduction in mitochondrial potential and cellular ATP, suggesting that atrophy resulted from depletion of glucose-derived metabolic substrates. Expression of the antiapoptotic protein, Bcl-X(L), prevented death but not atrophy following either growth factor or glucose withdrawal. In Bcl-X(L) transgenic animals, size and metabolic activity of naive T cells were regulated through the TCR and correlated with TCR-dependent glut1 expression. These data suggest that ligands for cell-specific receptors promote cell survival by regulating nutrient uptake and utilization.
在没有受体刺激的情况下，多细胞生物的细胞会通过凋亡死亡。在此我们表明，缺乏受体刺激的淋巴细胞在发生凋亡之前会经历渐进性萎缩。受体结合丧失后，淋巴细胞迅速下调葡萄糖转运蛋白glut1。这伴随着线粒体膜电位和细胞ATP的降低，表明萎缩是由葡萄糖衍生的代谢底物耗竭所致。抗凋亡蛋白Bcl-X(L)的表达可防止生长因子或葡萄糖撤除后的细胞死亡，但不能防止萎缩。在Bcl-X(L)转基因动物中，初始T细胞的大小和代谢活性通过TCR进行调节，并与TCR依赖性glut1表达相关。这些数据表明，细胞特异性受体的配体通过调节营养物质的摄取和利用来促进细胞存活。
