Gonin-Giraud S, Mathieu A-L, Diocou S, Tomkowiak M, Delorme G, Marvel J
Immuno-Apoptose, INSERM U503, Centre d'études et de Recherches en Virologie et en Immunologie, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Cell Death Differ. 2002 Oct;9(10):1147-57. doi: 10.1038/sj.cdd.4401079.
IL-3 regulates the glycolytic pathway. In Baf-3 cells IL-3 starvation leads to a decrease in glucose uptake and in lactate production. To determine if there is a link between the decreased metabolism induced by growth factor-starvation and the induction of cell death, we have compared the cell death characteristics and the metabolic modifications induced by IL-3-deprivation or glucose-deprivation in Baf-3 cells. We show that in both conditions cells die by an apoptotic process which involves the activation of similar Caspases. Different metabolic parameters (i.e. intracellular ATP levels and lactate accumulation in the culture medium) were measured. We show that IL-3 deprivation leads to a partial decrease in lactate production in contrast to glucose deprivation that completely inhibits lactate production. Similarly following IL-3-starvation a significant drop in the intracellular ATP levels in live cells is observed only after 16 h when a large fraction, more than 50 per cent of cells, is already apoptotic. On the contrary, glucose deprivation is followed by an abrupt decrease in ATP levels in the first 2 h of treatment. However, in the presence of IL-3, cells are able to survive for an extended time in these conditions since 70% of cells survived with low ATP levels for up to 16 h. This was not due to partial inhibition of the apoptotic process by the low level of ATP as glucose-deprivation in the absence of IL-3 led to faster death kinetics of Baf-3 cells compared with IL-3 starvation only. These results indicate that the drop in ATP levels and the triggering of apoptosis can be dissociated in time and that when the glycolytic pathway is strongly inhibited, cells are able to survive with relatively low ATP levels if IL-3 is present. Finally we show that induction of bcl-x by IL-3 protects cells from glucose-deprivation induced cell death.
白细胞介素-3调节糖酵解途径。在BaF-3细胞中，白细胞介素-3饥饿导致葡萄糖摄取和乳酸生成减少。为了确定生长因子饥饿诱导的代谢降低与细胞死亡诱导之间是否存在联系，我们比较了BaF-3细胞中白细胞介素-3剥夺或葡萄糖剥夺诱导的细胞死亡特征和代谢改变。我们发现，在这两种情况下，细胞均通过凋亡过程死亡，该过程涉及相似的半胱天冬酶的激活。我们测量了不同的代谢参数（即细胞内ATP水平和培养基中乳酸积累）。我们发现，与完全抑制乳酸生成的葡萄糖剥夺相反，白细胞介素-3剥夺导致乳酸生成部分减少。同样，在白细胞介素-3饥饿后，仅在16小时后才观察到活细胞中细胞内ATP水平显著下降，此时很大一部分（超过50%）细胞已经凋亡。相反，在处理的前2小时内，葡萄糖剥夺后ATP水平急剧下降。然而，在存在白细胞介素-3的情况下，细胞能够在这些条件下存活更长时间，因为70%的细胞在低ATP水平下存活长达16小时。这不是由于低水平的ATP对凋亡过程的部分抑制，因为在没有白细胞介素-3的情况下葡萄糖剥夺导致BaF-3细胞的死亡动力学比仅白细胞介素-3饥饿更快。这些结果表明，ATP水平的下降和凋亡的触发在时间上可以分离，并且当糖酵解途径受到强烈抑制时，如果存在白细胞介素-3，细胞能够在相对较低的ATP水平下存活。最后，我们发现白细胞介素-3诱导的bcl-x可保护细胞免受葡萄糖剥夺诱导的细胞死亡。
