钙离子信号与细胞凋亡

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。

Calcium Signaling in Apoptosis

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.