Calcium and Apoptosis

Abstract

Calcium ion is an important secondary messenger in controlling cell death. The role of calcium in apoptotic signaling has been extensively investigated in recent years. Our overall understanding on this topic, however, is still far from complete. In fact, results of some of the earlier studies were somewhat controversial. Only in recent years, the role of Ca²⁺ signaling in apoptosis has become clear. In this review, we summarize some of the major aspects of Ca²⁺ signaling in apoptosis based on our own studies as well as those reported in the recent literature. This review includes four major parts: In Part 1, we give an overview of cell death and a summary of the essential apoptotic signaling pathways. In Part 2, we discuss the role of Ca²⁺ signaling in programmed cell death. Particularly, we presented the evidence that Ca²⁺ signal plays a role in the upstream of the mitochondria-dependent apoptotic pathway. In Part 3, we summarize the recent evidence suggesting possible interactions between the Ca²⁺ signal and Bcl-2 family proteins, which are well-known regulators of the apoptotic process. Finally, in Part 4, we summarize recent findings on some of the Ca²⁺-regulating proteins that provide possible molecular pathways connecting Ca²⁺ signaling with ROS-induced neuronal cell death. We hope that, a better understanding of the Ca²⁺ signaling pathways may lead to the development of novel therapeutic approaches for major neurodegenerative diseases.