Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support
Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support
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DOI：
10.1002/jcb.10449
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发表时间：
2003-04-01
影响因子：
4
通讯作者：
Bierer, BE
中科院分区：
文献类型：
--
作者：
Morley, SC;Sun, GP;Bierer, BE
我们先前已经证明，使用茉莉素内酯，肌动蛋白细胞骨架的稳定增强了细胞因子戒断诱导的细胞凋亡(Posey and Bierer [1999] J. Bierer。化学274:4259 - 4265)。然而，仍然有可能的是，肌动蛋白动力学调节的中断，而不仅仅是f -肌动蛋白的稳定，是影响凋亡信号转导的必要条件。我们现在已经测试了细胞松弛素D的作用，它是一种促进肌动蛋白解聚的特化剂。在研究的时间过程中，肌动蛋白解聚不影响CD95 （Fas）诱导的Jurkat T细胞死亡，但确实增强了因子依赖性细胞系对细胞因子戒断诱导的凋亡的承诺。细胞死亡的诱导不是直接的细胞骨架崩溃的结果，因为在存在IL-2的情况下用细胞松弛素D处理细胞并不促进死亡。与jasplakinolide一样，过度表达抗凋亡蛋白Bcl-x(L)可延迟细胞凋亡承诺的增强，但与jasplakinolide不同的是，细胞松弛素D也适度影响细胞凋亡的“执行”阶段。综上所述，这些结果表明，肌动蛋白动力学的变化，即肌动蛋白聚合和解聚的速度，调节了凋亡信号的转导，使淋巴细胞从所需的生长因子中退出，进入死亡途径。2003年Wiley-Liss出版（匕首）。
We have previously shown, using jasplakinolide, that stabilization of the actin cytoskeleton enhanced apoptosis induced upon cytokine withdrawal (Posey and Bierer [1999] J. Biol. Chem. 274:4259-4265). It remained possible, however, that a disruption in the regulation of actin dynamics, and not simply F-actin stabilization, was required to affect the transduction of an apoptotic signal. We have now tested the effects of cytochalasin D, awe I I-characterized agent that promoted actin depolymerization. Actin depolymerization did not affect CD95 (Fas)-induced death of Jurkat T cells in the time course studied but did enhance the commitment to cytokine withdrawal-induced apoptosis of factor-dependent cell lines. The induction of cell death was not the result of direct cytoskeletal collapse, since treatment of the cells with cytochalasin D in the presence of IL-2 did not promote death. As with jasplakinolide, the enhancement of commitment to apoptosis could be delayed by overexpression of the anti-apoptotic protein Bcl-x(L), but, unlike jasplakinolide, cytochalasin D modestly affected the "execution" stage of apoptosis as well. Taken together, these results suggest that changes in actin dynamics, i.e., the rate of actin polymerization and depolymerization, modulate the transduction of the apoptotic signal committing lymphocytes, withdrawn from required growth factors, to the death pathway. Published 2003 Wiley-Liss, Inc.(dagger).