Nicotera P, Leist M, Ferrando-May E
Chair of Molecular Toxicology, Faculty of Biology, University of Konstanz, Germany.
Toxicol Lett. 1998 Dec 28;102-103:139-42. doi: 10.1016/s0378-4274(98)00298-7.
Regardless of whether apoptosis or necrosis are elicited by toxicants or by pathophysiological conditions they are considered conceptually distinct forms of cell death. Nevertheless, there is increasing evidence that classical apoptosis and necrosis represent only the extreme ends of a wide range of possible morphological and biochemical deaths. The two classical types of demise can occur simultaneously in tissues or cell cultures exposed to the same stimulus and often, the intensity of the same initial insult decides the prevalence of either apoptosis or necrosis. The execution of the death program seems to involve a relatively limited number of pathways. In many instances, their ordered execution results in characteristic morphological and biochemical changes termed apoptosis. However, some subroutines of the degradation program may not be active in all cases of cell death. Then, the morphological appearance of dying cells and some of their biochemical alterations differ from those of classical apoptosis. We have recently shown that intracellular energy levels and mitochondrial function are rapidly compromised in necrosis, but not in apoptosis of neuronal cells. Then we went on to show that pre-empting human T cells of ATP switches the type of demise caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) from apoptosis to necrosis. Conditions of controlled intracellular ATP depletion, which was obtained by blocking mitochondrial and/or glycolytic ATP generation were used in combination with repletion of the cytosolic ATP pool with glucose to redirect the death program towards apoptosis or necrosis.
无论凋亡或坏死是由毒物引起还是由病理生理状况引起，它们在概念上都被视为细胞死亡的不同形式。然而，越来越多的证据表明，经典的凋亡和坏死仅仅代表了一系列广泛的可能的形态学和生物化学死亡形式的极端情况。在暴露于相同刺激的组织或细胞培养物中，这两种经典的死亡类型可能同时发生，而且通常，相同初始损伤的强度决定了凋亡或坏死的发生率。死亡程序的执行似乎涉及相对有限的一些途径。在许多情况下，它们的有序执行会导致称为凋亡的特征性形态学和生物化学变化。然而，降解程序的一些子程序在所有细胞死亡情况下可能并不活跃。那么，垂死细胞的形态外观及其一些生物化学改变就与经典凋亡不同。我们最近发现，在坏死过程中，细胞内能量水平和线粒体功能会迅速受损，但在神经元细胞的凋亡过程中则不会。然后我们继续表明，剥夺人类T细胞的ATP会将两种经典凋亡触发因素（星形孢菌素和CD95刺激）所导致的死亡类型从凋亡转变为坏死。通过阻断线粒体和/或糖酵解ATP生成获得的细胞内ATP受控耗竭条件，与用葡萄糖补充胞质ATP池相结合，用于将死亡程序导向凋亡或坏死。
