Leist M, Single B, Castoldi A F, Kühnle S, Nicotera P
Department of Molecular Toxicology, Faculty of Biology, University of Konstanz, Germany.
J Exp Med. 1997 Apr 21;185(8):1481-6. doi: 10.1084/jem.185.8.1481.
Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.
细胞凋亡和坏死在概念和形态上被认为是不同形式的细胞死亡。在此，我们报告，当人类T细胞被剥夺三磷酸腺苷（ATP）时，由两种经典凋亡触发因素（星形孢菌素和CD95刺激）导致的细胞死亡从凋亡转变为坏死。在预先耗尽ATP并用两种诱导剂之一处理的细胞中，未发生核浓缩和DNA片段化，尽管细胞死亡动力学未改变。用葡萄糖对线粒体外ATP池进行选择性和分级补充可防止坏死，并恢复细胞进行凋亡的能力。ATP脉冲/耗尽/补充实验还表明，糖酵解或线粒体产生ATP对于凋亡最后阶段的有效执行是必需的，该阶段涉及核浓缩和DNA降解。
