Centro Andaluz de Biología del Desarrollo (CABD), and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas, Universidad Pablo de, Carretera de Utrera Km 1, 41013 Sevilla, Spain.
Grupo de Neurodesarrollo, Unidad de Gestión de Pediatría, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain.
Int J Mol Sci. 2017 Nov 11;18(11):2393. doi: 10.3390/ijms18112393.
During apoptosis, cells undergo characteristic morphological changes in which the cytoskeleton plays an active role. The cytoskeleton rearrangements have been mainly attributed to actinomyosin ring contraction, while microtubule and intermediate filaments are depolymerized at early stages of apoptosis. However, recent results have shown that microtubules are reorganized during the execution phase of apoptosis forming an apoptotic microtubule network (AMN). Evidence suggests that AMN is required to maintain plasma membrane integrity and cell morphology during the execution phase of apoptosis. The new "two coffins" hypothesis proposes that both AMN and apoptotic cells can adopt two morphological patterns, round or irregular, which result from different cytoskeleton kinetic reorganization during the execution phase of apoptosis induced by genotoxic agents. In addition, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocyte responses. These findings suggest that knowing the type of apoptosis may be important to predict how fast apoptotic cells undergo secondary necrosis and the subsequent immune response. From a pathological point of view, round-shaped apoptosis can be seen as a physiological and controlled type of apoptosis, while irregular-shaped apoptosis can be considered as a pathological type of cell death closer to necrosis.
在细胞凋亡过程中，细胞会发生特征性的形态变化，细胞骨架在此过程中发挥着积极作用。细胞骨架的重排主要归因于肌动球蛋白环的收缩，而微管和中间丝在细胞凋亡的早期阶段被解聚。然而，最近的研究结果表明，微管在细胞凋亡的执行阶段会重新组织，形成凋亡微管网络（AMN）。有证据表明，在细胞凋亡的执行阶段，AMN 对于维持质膜完整性和细胞形态是必需的。新的“两个棺材”假说提出，AMN 和凋亡细胞都可以采用两种形态模式，即圆形或不规则形，这是由不同的细胞骨架动力学在由遗传毒性药物诱导的细胞凋亡的执行阶段发生的重排所导致的。此外，圆形和不规则形状的凋亡在 AMN 的维持、质膜完整性和吞噬细胞反应方面表现出不同的生物学特性。这些发现表明，了解凋亡的类型可能对于预测凋亡细胞在多大程度上快速发生继发性坏死和随后的免疫反应是很重要的。从病理学的角度来看，圆形的凋亡可以被视为一种生理的和受控的凋亡类型，而不规则形状的凋亡可以被视为更接近坏死的病理类型的细胞死亡。
