钙离子信号与细胞凋亡

CALCIUM SIGNALING IN APOPTOSIS

细胞凋亡的分子机制是什么?这个问题当前引起人们广泛的研究兴趣。作为重要的第二信使,钙信号在许多生理和细胞活动中都起到了十分重要的作用。钙信号是否也在凋亡的调控中起作用呢?虽然在过去十多年中,许多研究证据都表明钙信号参与凋亡的调控,但是,钙信号如何作用于凋亡过程的具体机理仍然是众说纷纭。事实上,许多研究结果仍存有争议。文章总结了近几年来大量关于钙信号与凋亡研究的成果,集中讨论了两个问题1)在凋亡前期“决定阶段”有没有钙离子信号的参与?2)钙离子信号与哪些凋亡调控因子(包括Bcl-2族蛋白)相互作用及如何作用?这问题还牵涉到亚细胞结构中钙库的作用(包括细胞质、内质网和线粒体)。根据作者自己的实验结果,文章对这些文献中不同的说法作了一些具体的评估。最后,文章还提出了一个钙离子信号参与调控细胞凋亡的可能模型。

What are the molecular mechanisms by which apoptosis is regulated by external or internal signals? This problem is under active investigation at present. As a major second messenger, Ca2+ signal is known to be a key player in the regulation of many physiological and cellular processes. Does Ca2+ signal also have a role in the regulation of apoptosis? Evidence implicating the involvement of Ca2+ in apoptosis has been reported during the past decade from many studies. The detailed mechanisms concerning how Ca2+ signals may interact with the apoptotic machinery, however, are still not very clearly understood yet. Results from different studies did not always give a consistent picture and sometimes might even be contradictory. In this review, the authors tried to summarize recent studies on Ca2+ signaling in apoptosis to address two main questions: 1) Whether Ca2+ signaling is involved in the commitment phase of apoptosis? 2) How may Ca2+ signaling interact with the signaling pathway of apoptosis (including Bcl-2 family proteins)? They also discussed the roles of various pools of Ca2+ stored in different subcellular compartments (including cytosolic Ca2+, ER Ca2+ and mitochondrial Ca2+) on the apoptotic process. Based on results from their own studies, they also tried to give a fair evaluation on the various proposed mechanisms suggested in the literatures. Finally, a model summarizing the possible pathways of Ca2+ signaling in apoptosis was given in this review.