Berridge M V, Tan A S, McCoy K D, Kansara M, Rudert F
Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington, New Zealand.
J Immunol. 1996 Jun 1;156(11):4092-9.
Treatment of activated human T cells with CD95 (Fas/Apo-1) ligand or Abs against CD95 results in apoptotic cell death. Although cellular responses to CD95 ligation have been described in some detail, the early molecular events that result in T cell death are only now beginning to be elucidated. Using Jurkat cells as a model of activated human T cells, we have investigated the effects of CD95 ligation on glucose transport and on glucose transporter function. We show that within minutes of CD95 activation, the ability to transport glucose across the plasma membrane is compromised and that transient exposure to Abs against CD95 for as little as 3 min results in reduced glucose transport and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) responses measured at 16 h. The effects of CD95 ligation on glucose transport are shown to be associated with loss of affinity of glucose transporters for glucose without altered maximum velocity and without changes in the cell surface expression of Glut 1, the predominant glucose transporter isotype on Jurkat cells. These results support a model of CD95 induced cell death that, at least in its early stages, does not depend on signaling to the nucleus or on macromolecular synthesis. Acute regulation of glucose transport is proposed to be an early effector mechanism in CD95-induced apoptotic cell death.
用CD95（Fas/Apo-1）配体或抗CD95抗体处理活化的人T细胞会导致细胞凋亡性死亡。尽管已经较为详细地描述了细胞对CD95连接的反应，但导致T细胞死亡的早期分子事件直到现在才开始得到阐明。我们以Jurkat细胞作为活化的人T细胞模型，研究了CD95连接对葡萄糖转运和葡萄糖转运蛋白功能的影响。我们发现，在CD95激活后的几分钟内，葡萄糖跨质膜转运的能力就受到损害，并且短暂暴露于抗CD95抗体仅3分钟就会导致葡萄糖转运减少以及在16小时时测得的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）反应降低。CD95连接对葡萄糖转运的影响显示与葡萄糖转运蛋白对葡萄糖的亲和力丧失有关，而最大速度未改变，并且Jurkat细胞上主要的葡萄糖转运蛋白亚型Glut 1的细胞表面表达也没有变化。这些结果支持了一种CD95诱导细胞死亡的模型，即至少在其早期阶段，不依赖于向细胞核的信号传导或大分子合成。葡萄糖转运的急性调节被认为是CD95诱导的凋亡性细胞死亡中的一种早期效应机制。
