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细胞凋亡过程中Smac/DIABLO释放的实时单细胞分析

Real-time single cell analysis of Smac/DIABLO release during apoptosis.

作者信息

Rehm Markus, Düssmann Heiko, Prehn Jochen H M

机构信息

Interdisciplinary Center for Clinical Research, University Münster Clinics, Münster, Germany.

出版信息

J Cell Biol. 2003 Sep 15;162(6):1031-43. doi: 10.1083/jcb.200303123.

DOI:10.1083/jcb.200303123
PMID:12975347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2172837/
Abstract

We examined the temporal and causal relationship between Smac/DIABLO release, cytochrome c (cyt-c) release, and caspase activation at the single cell level during apoptosis. Cells treated with the broad-spectrum caspase inhibitor z-VAD-fmk, caspase-3 (Casp-3)-deficient MCF-7 cells, as well as Bax-deficient DU-145 cells released Smac/DIABLO and cyt-c in response to proapoptotic agents. Real-time confocal imaging of MCF-7 cells stably expressing Smac/DIABLO-yellow fluorescent protein (YFP) revealed that the average duration of Smac/DIABLO-YFP release was greater than that of cyt-c-green fluorescent protein (GFP). However, there was no significant difference in the time to the onset of release, and both cyt-c-GFP and Smac/DIABLO-YFP release coincided with mitochondrial membrane potential depolarization. We also observed no significant differences in the Smac/DIABLO-YFP release kinetics when z-VAD-fmk-sensitive caspases were inhibited or Casp-3 was reintroduced. Simultaneous measurement of DEVDase activation and Smac/DIABLO-YFP release demonstrated that DEVDase activation occurred within 10 min of release, even in the absence of Casp-3.

摘要

我们在细胞凋亡过程中，于单细胞水平研究了Smac/DIABLO释放、细胞色素c（cyt-c）释放与半胱天冬酶激活之间的时间和因果关系。用广谱半胱天冬酶抑制剂z-VAD-fmk处理的细胞、半胱天冬酶-3（Casp-3）缺陷的MCF-7细胞，以及Bax缺陷的DU-145细胞，在受到促凋亡剂刺激时会释放Smac/DIABLO和cyt-c。对稳定表达Smac/DIABLO-黄色荧光蛋白（YFP）的MCF-7细胞进行实时共聚焦成像显示，Smac/DIABLO-YFP释放的平均持续时间长于cyt-c-绿色荧光蛋白（GFP）。然而，释放开始的时间没有显著差异，并且cyt-c-GFP和Smac/DIABLO-YFP的释放都与线粒体膜电位去极化同时发生。当z-VAD-fmk敏感的半胱天冬酶被抑制或重新引入Casp-3时，我们也观察到Smac/DIABLO-YFP释放动力学没有显著差异。同时测量DEVD酶激活和Smac/DIABLO-YFP释放表明，即使在没有Casp-3的情况下，DEVD酶激活也会在释放后10分钟内发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/ea2a157e14ca/200303123f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/50c3adea8713/200303123f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/9456686a1967/200303123f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/bd35c1ac21c0/200303123f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/3e38affe4db0/200303123f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/87d888d7fb78/200303123f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/ea2a157e14ca/200303123f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/50c3adea8713/200303123f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/ace3404e36c8/200303123f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/de2a0f310bf4/200303123f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/9456686a1967/200303123f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/bd35c1ac21c0/200303123f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/3e38affe4db0/200303123f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/87d888d7fb78/200303123f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3093/2172837/ea2a157e14ca/200303123f8.jpg

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