The cleavage mode of apoptotic nuclear vesiculation is related to plasma membrane blebbing and depends on actin reorganization

In U937 monocytic cells induced to apoptosis, plasma membrane blebbing of different intensities appears, before the development of nuclear alterations; this latter phenomenon can occur through two major pathways, namely the cleavage and the budding mode (Dini et al., 1996). Strongly blebbing cells develop deep nuclear constrictions leading to nuclear fragmentation according to the cleavage mode, while cells with milder forms of blebbing, or no blebbing at all, undergo nuclear fragmentation along the budding mode. Compounds interfering with different cytoskeletal components affect blebbing, which is completely inhibited by the actin polymerization inhibitors, cytochalasins, while disturbance of tubulin network with taxol limits blebbing to milder forms. At the same time, the cytoskeletal poisons affect the type of nuclear fragmentation, abolishing the cleavage mode, shifting all events into the budding pathway. Adherent cells, which possess a more structured cytoskeleton, do not develop strong blebs and undergo nuclear fragmentation via budding. These observations suggest that the deep cytoskeletal movements that cause the strongest forms of plasma membrane blebbing strangle the nucleus, leading to the constrictions that later evolve into nuclear fragmentation by cleavage. The trigger for the cytoskeletal movements, known to be redox-sensitive, is probably the apoptotic GSH extrusion.