文章：

糖皮质激素诱导的细胞死亡是通过降低淋巴细胞的糖代谢介导的

Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells

原文发布日期：2011-07-29

DOI: 10.1038/bcj.2011.27

类型: Original Article

开放获取: 是

英文摘要：

Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.

摘要翻译： 

已知恶性细胞具有葡萄糖摄取增加和葡萄糖代谢加速的特点。通过使用液相色谱和质谱分析，我们发现用糖皮质激素地塞米松处理急性淋巴细胞白血病细胞可显著抑制糖酵解。由此我们证明，地塞米松降低了白血病细胞的葡萄糖消耗、葡萄糖利用和葡萄糖摄取。此外，地塞米松处理降低了质膜相关葡萄糖转运蛋白GLUT1的水平，从而揭示了抑制葡萄糖摄取的机制。在急性淋巴细胞白血病细胞系和体外培养的患者白血病原始细胞中，葡萄糖摄取的抑制与细胞死亡的诱导相关。在RS4;11细胞中加入二甲基琥珀酸可部分克服地塞米松诱导的细胞死亡，这进一步支持了抑制糖酵解有助于诱导细胞凋亡的观点。最后，当在较低葡萄糖浓度下培养时，地塞米松杀死RS4;11细胞的效率显著更高，这表明葡萄糖水平的调节可能会影响糖皮质激素治疗急性淋巴细胞白血病的有效性。总之，我们的数据表明，糖皮质激素治疗阻断了白血病细胞对葡萄糖的摄取，导致糖酵解抑制，而这些效应在这些药物诱导细胞死亡的过程中起着重要作用。

原文链接：

Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells