Early changes in metabolism of leukemic cell lines upon induction of apoptosis by cytotoxic drugs.
Early changes in metabolism of leukemic cell lines upon induction of apoptosis by cytotoxic drugs.
复制标题
细胞毒性药物诱导细胞凋亡后白血病细胞系代谢的早期变化。
DOI：
10.1016/s0014-2999(03)01425-0
复制
发表时间：
2003
影响因子：
5
通讯作者：
Modiano,JaimeF
中科院分区：
文献类型：
--
作者：
Khare,Sangeeta;Banai,Yona;Gokulan,Kuppan;Smith3rd,Roger;Linthicum,DarwinS;Modiano,JaimeF
我们评估了喜树碱或紫杉醇处理的人U937和K562白血病细胞胞外酸化率的实时变化。喜树碱或紫杉醇处理U937细胞30-60分钟后，对阿米洛利敏感的胞外酸化速率出现不可逆的持续下降。相反，暴露于叠氮钠的U937细胞显示细胞外酸化速率立即急剧下降，这种下降在叠氮停药后是可逆的。K562细胞需要20倍以上的喜树碱来促进细胞外酸化速率的类似变化，同时对喜树碱或紫杉醇诱导的细胞凋亡的敏感性也具有相应的抵抗力。这些数据表明，细胞不可逆的凋亡承诺与迅速的代谢变化有关，这种变化反映在胞外酸化速率的降低，并受Na+/H+逆向转运体的调节。此外，胞外酸化速率变化的检测并不局限于特定的细胞类型或凋亡途径，这使其成为筛选化合物促凋亡活性的潜在有用工具。
We evaluated real-time changes in extracellular acidification rates of human U937 and K562 leukemic cells treated with camptothecin or taxol. U937 cells treated with camptothecin or taxol for 30–60 min showed a continuous, irreversible decrease in extracellular acidification rate that was sensitive to amiloride. In contrast, U937 cells exposed to sodium azide showed an immediate, steep decrease in extracellular acidification rate that was reversible upon azide withdrawal. K562 cells required a >20-fold higher dose of camptothecin to promote similar changes in the extracellular acidification rate, with a corresponding resistance in their susceptibility to camptothecin- or taxol-induced apoptosis. The data show that irreversible commitment to apoptosis is associated with rapid metabolic changes that are reflected by decreased extracellular acidification rate and regulated by the Na+/H+antiporter. Moreover, detection of extracellular acidification rate changes was not restricted to a particular cell type or apoptosis pathway, making this a potentially useful tool to screen compounds for pro-apoptotic activity.