Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death
Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death
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DOI：
10.1242/jcs.017343
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发表时间：
2008-02-01
影响因子：
4
通讯作者：
Sontheimer, Harald
中科院分区：
文献类型：
--
作者：
Ernest, Nola Jean;Habela, Christa W.;Sontheimer, Harald
程序性细胞死亡（凋亡）在组织维持中是重要的。细胞凋亡的标志包括半胱天冬酶激活、DNA片段化和细胞体积的总体减少。这种凋亡体积减少（AVD）是否仅仅是对凋亡引发剂的反应，或者它是否具有功能意义尚不清楚。在这项研究中，我们试图回答这个问题，使用人类恶性胶质瘤细胞作为模型系统。在体内，高级别胶质瘤表现出凋亡细胞百分比增加以及死亡配体受体上调。通过动态监测细胞体积，我们表明，诱导凋亡，通过激活无论是内在或外在途径与星形孢菌素或TRAIL，分别导致在D54-MG人胶质瘤细胞中的快速AVD。这种细胞体积的减少可以通过抑制Cl-通过通道的流出来防止。AVD的这种抑制也减少了半胱天冬酶3、8和9的活化，并抑制了DNA片段化。重要的是，即使在不存在死亡配体的情况下，将细胞体积减少至原始体积的70%持续至少3小时的时间段的实验操作也足以引发细胞凋亡。因此，该数据表明细胞浓缩对于诱导细胞凋亡是必要且充分的。
Programmed cell death ( apoptosis) is important in tissue maintenance. Hallmarks of apoptosis include caspase activation, DNA fragmentation and an overall reduction in cell volume. Whether this apoptotic volume decrease (AVD) is a mere response to initiators of apoptosis or whether it is functionally significant is not clear. In this study, we sought to answer this question using human malignant glioma cells as a model system. In vivo, high grade gliomas demonstrate an increased percentage of apoptotic cells as well as upregulation of death ligand receptors. By dynamically monitoring cell volume, we show that the induction of apoptosis, via activation of either the intrinsic or extrinsic pathways with staurosporine or TRAIL, respectively, resulted in a rapid AVD in D54-MG human glioma cells. This decrease in cell volume could be prevented by inhibiting the efflux of Cl- through channels. Such suppression of AVD also reduced the activation of caspases 3, 8 and 9 and suppressed DNA fragmentation. Importantly, experimental manipulations that reduce the cell volume to 70% of the original volume for periods of at least 3 hours were sufficient to initiate apoptosis even in the absence of death ligands. Hence, this data suggests that cell condensation is both necessary and sufficient for the induction of apoptosis.