Cyclic Luciferase for Real-Time Sensing of Caspase-3 Activities in Living Mammals

摘要

Eukaryotic cells contain many proteases involved in cell growth, division, differentiation, migration, and intra- or extracellular signaling. One of the complicated proteolytic signaling processes is used to decide programmed cell death or apoptosis. Improper apoptosis causes many diseases including Alzheimer's disease, Huntington's disease, ischae-mia, autoimmune disorders, and immortality of cancer cells. As cytosolic caspases play a central role in mediating the initiation and propagation of apoptosis, chemical compounds that can either inhibit or accelerate caspase activity are a major concern. Also, an understanding of the physiological proteolytic processes inside living organisms is of crucial importance for assessing the roles of proteases in normal states and diseases. Hence, the development of a rapid screening system to detect caspase activity and a noninvasive method to image apoptosis is essential for the discovery of novel compounds that are potential therapeutic chemicals. These developments would provide new insights into the mechanism of apoptosis.