Delay in Apoptosome Formation Attenuates Apoptosis in Mouse Embryonic Stem Cell Differentiation
Delay in Apoptosome Formation Attenuates Apoptosis in Mouse Embryonic Stem Cell Differentiation
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DOI：
10.1074/jbc.m113.536730
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发表时间：
2014-06-13
影响因子：
4.8
通讯作者：
Baharvand, Hossein
中科院分区：
文献类型：
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作者：
Akbari-Birgani, Shiva;Hosseinkhani, Saman;Baharvand, Hossein
分化是多细胞生物发育中不可分割的过程。小鼠胚胎干细胞（mESC）是进行细胞分化体外研究的宝贵研究工具。细胞凋亡作为一种众所周知的细胞死亡机制，显示出与细胞分化的一些共同特征，这在该领域引起了许多歧义。这里的研究问题是细胞如何区分这两个过程。我们研究了线粒体凋亡途径和细胞能量水平在 mESC 分化为心肌细胞及其凋亡过程中的作用。在诱导细胞凋亡和分化时观察到 p53 表达、细胞色素 c 释放、凋亡体形成和 caspase-3/7 激活。然而，在诱导这两个过程时，在细胞色素 c 出现的时间、凋亡体形成和 caspase 活性方面检测到显着差异。在细胞凋亡中，细胞色素 c 释放后迅速观察到凋亡体形成和 caspase 活性。与细胞凋亡不同，分化时细胞色素c的释放需要更多时间，并且最大caspase活性也推迟了24小时。这种延迟表明在 mESC 分化为心肌细胞的过程中存在调节机制。细胞的ATP含量在细胞色素c释放后立即观察到最高，诱导凋亡后6小时，然后下降，但直到分化后48小时逐渐增加。这些观察结果表明，细胞色素 c 释放的延迟或 ATP 的延迟增加会减弱凋亡体的形成，并且 caspase 激活从而区分 mESC 中的凋亡和分化。
Differentiation is an inseparable process of development in multicellular organisms. Mouse embryonic stem cells (mESCs) represent a valuable research tool to conduct in vitro studies of cell differentiation. Apoptosis as a well known cell death mechanism shows some common features with cell differentiation, which has caused a number of ambiguities in the field. The research question here is how cells could differentiate these two processes from each other. We have investigated the role of the mitochondrial apoptotic pathway and cell energy level during differentiation of mESCs into the cardiomyocytes and their apoptosis. p53 expression, cytochrome c release, apoptosome formation, and caspase-3/7 activation are observed upon induction of both apoptosis and differentiation. However, remarkable differences are detected in time of cytochrome c appearance, apoptosome formation, and caspase activity upon induction of both processes. In apoptosis, apoptosome formation and caspase activity were observed rapidly following the cytochrome c release. Unlike apoptosis, the release of cytochrome c upon differentiation took more time, and the maximum caspase activity was also postponed for 24 h. This delay suggests that there is a regulatory mechanism during differentiation of mESCs into cardiomyocytes. The highest ATP content of cells was observed immediately after cytochrome c release 6 h after apoptosis induction and then decreased, but it was gradually increased up to 48 h after differentiation. These observations suggest that a delay in the release of cytochrome c or delay in ATP increase attenuate apoptosome formation, and caspase activation thereby discriminates apoptosis from differentiation in mESCs.