Apoptosis of syncytia induced by the HIV-1-envelope glycoprotein complex: Influence of cell shape and size
Apoptosis of syncytia induced by the HIV-1-envelope glycoprotein complex: Influence of cell shape and size
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DOI：
10.1006/excr.2000.5062
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发表时间：
2000-11-25
影响因子：
3.7
通讯作者：
Kroemer, G
中科院分区：
文献类型：
--
作者：
Ferri, KF;Jacotot, E;Kroemer, G
当与CD 4（+）CXCR 4（+）细胞共培养时，稳定转染了嗜淋巴细胞HIV-1 Env基因的细胞形成合胞体。异核体然后自发地经历凋亡，同时表现出线粒体膜pemeabilization以及核染色质凝聚的迹象。通过在末端取代的烷基硫醇盐的自组装单层上生长合胞体来实现细胞几何形状的调节，所述自组装单层被设计为控制底物的粘附性质，通过在小的圆形粘附胰岛上培养合胞体来诱导合胞体的铺展（直径5 μ m），放置在细胞可以桥接的距离（10 μ m）处，抑制自发的和星形孢菌素诱导的凋亡迹象，在线粒体和细胞核水平上，并允许产生较大的合胞体，瞬时细胞铺展赋予细胞凋亡抑制的记忆，其在采用常规细胞形状时是保守的。通过将合胞体培养在由非粘附区域分隔的、具有确定大小（400至2500 E mum（2））的方形平面粘附岛上来限制合胞体的大小，可以提高凋亡性细胞死亡的速率，如线粒体外膜的加速透化、线粒体内跨膜电位的丧失和核凋亡频率的增加所示。总之，合胞体的大小和形状的外部约束强烈调节其倾向进行凋亡。(C)北京大学出版社.
Cells stably transfected with a lymphotropic HIV-1 Env gene form syncytia when cocultured with CD4(+)CXCR4(+) cells. Heterokaryons then spontaneously undergo apoptosis, while manifesting signs of mitochondrial membrane pemeabilization as well as nuclear chromatin condensation. Modulation of cellular geometry was achieved by growing syncytia on self-assembled monolayers of terminally substituted alkanethiolates designed to control the adhesive properties of the substrates, Spreading of syncytia, induced by culturing them on small circular adhesive islets (diameter 5 mum), placed at a distance that cells can bridge (10 mum), inhibited spontaneous and staurosporin-induced signs of apoptosis, both at the mitochondrial and at the nuclear levels, and allowed for the generation of larger syncytia, Transient cell spreading conferred a memory of apoptosis inhibition which was conserved upon adoption of a conventional cell shape. Limiting syncytium size by culturing them on square-shaped planar adhesive islands of defined size (400 to 2500 E mum(2)), separated by nonadhesive regions, enhanced the rate of apoptotic cell death, as indicated by an accelerated permeabilization of the outer mitochondrial membrane, loss of the mitochondrial inner transmembrane potential, and an increased frequency of nuclear apoptosis. In conclusion, external constraints on syncytial size and shape strongly modulate their propensity to undergo apoptosis. (C) 2000 Academic Press.