McConkey D J
Department of Cell Biology-173, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Scanning Microsc. 1996;10(3):777-93; discussion 793-4.
The recognition that apoptosis is regulated by an evolutionarily conserved set of polypeptides from the nematode Caenorhabditis elegans to humans suggests that a conserved set of biochemical mechanism(s) may also be involved in the response. Early evidence suggested that the endogenous endonuclease implicated in apoptosis in most model systems is Ca(2+)-dependent, and subsequent work from a number of independent laboratories suggests that alterations in cytosolic Ca2+ homeostasis are one of the conserved biochemical pathways regulating the response. Molecular targets for Ca2+ are now being identified and include signal transduction intermediates, endonuclease(s) and proteases, and the enzymes involved in the maintenance of phospholipid asymmetry in the plasma membrane. Furthermore, interesting preliminary work suggests that BCL-2 suppresses apoptosis via a mechanism that is linked to intracellular Ca2+ compartmentalization, and it appears that Ca2+ alterations in some examples of apoptosis occur as the result of changes within the mitochondria. This review will summarize what is known about the role of Ca2+ in the regulation of apoptosis and discuss how Ca2+ might interact with some of the other biochemical signals implicated in cell death.
从线虫秀丽隐杆线虫到人类，细胞凋亡受一组进化上保守的多肽调控，这一认识表明，一组保守的生化机制可能也参与了这一反应。早期证据表明，在大多数模型系统中，参与细胞凋亡的内源性核酸内切酶是钙依赖性的，随后多个独立实验室的研究表明，胞质钙稳态的改变是调控该反应的保守生化途径之一。钙的分子靶点目前正在被确定，包括信号转导中间体、核酸内切酶和蛋白酶，以及参与维持质膜磷脂不对称性的酶。此外，有趣的初步研究表明，BCL-2通过一种与细胞内钙区室化相关的机制抑制细胞凋亡，而且在某些细胞凋亡实例中，钙的改变似乎是线粒体内部变化的结果。本综述将总结关于钙在细胞凋亡调控中的作用的已知信息，并讨论钙可能如何与其他一些与细胞死亡相关的生化信号相互作用。
