Microfilament-disrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis.
Microfilament-disrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis.
复制标题
DOI：
--
复制
发表时间：
1992-02
期刊：
影响因子：
11.2
通讯作者：
Thomas G. Cotter;Seamus V. Lennon;Jacqueline M. Glynn;Douglas R. Green
中科院分区：
文献类型：
--
作者：
Thomas G. Cotter;Seamus V. Lennon;Jacqueline M. Glynn;Douglas R. Green
细胞凋亡是细胞死亡的一种形式，其中细胞“参与”，使得死亡发生需要代谢能量和通常的蛋白质合成。一旦开始，细胞凋亡的过程以有序的方式进行。在最早期发生DNA片段化，伴随着细胞收缩和内质网扩张。随后是细胞分裂，形成密封的膜囊泡，称为凋亡小体。在本研究中，我们已经证明，真菌代谢产物细胞松弛素B抑制细胞分裂和凋亡小体的形成，可能是通过其干扰肌动蛋白聚合的能力。当HL-60细胞用细胞松弛素B预处理，然后暴露于多种凋亡诱导剂中的一种时，包括UV照射、喜树碱、aphidocholin或PMA加离子霉素，可以观察到这种效应。观察到的效应并非HL-60细胞所特有，因为Molt-4和U-937细胞系也观察到了这种效应。细胞松弛素B对细胞凋亡早期的DNA断裂没有影响，对细胞核断裂也没有抑制作用。星形孢菌素的作用与细胞松弛素B相似，可能是由于其抑制蛋白激酶C的能力，蛋白激酶C是一种已知的微丝组装增效剂。这些数据表明，在细胞凋亡过程的后期阶段，微丝组装对于细胞凋亡体的形成是必要的。
Apoptosis is a form of cell death in which the cell "participates," such that metabolic energy and often protein synthesis are required for the death to occur. Once begun, the process of apoptosis proceeds in an ordered fashion. In the earliest phase DNA fragmentation occurs, accompanied by cell shrinkage and dilation of the endoplasmic reticulum. This is followed by cell fragmentation with the formation of sealed membrane vesicles, termed apoptotic bodies. In the present study we have demonstrated that the fungal metabolite cytochalasin B inhibits cell fragmentation and the formation of apoptotic bodies, probably by its ability to interfere with actin polymerization. This effect was seen when HL-60 cells were pretreated with cytochalasin B and then exposed to one of a number of apoptosis-inducing agents, including UV irradiation, camptothecin, aphidocholin, or PMA plus ionomycin. The observed effect was not peculiar to HL-60 cells, inasmuch as it was also seen for both Molt-4 and U-937 cell lines. Cytochalasin B had no effect on DNA fragmentation occurring in the earliest stage of apoptosis, and it appeared to have no inhibitory effects on nuclear fragmentation. Staurosporin had an effect similar to that seen with cytochalasin B, probably due to its ability to inhibit protein kinase C, which is a known potentiator of microfilament assembly. These data demonstrate that microfilament assembly is necessary for the formation of apoptotic bodies in the later stages of the apoptotic process.