Role of Calpain in Apoptosis

Apoptosis, a form of programmed cell death that occurs under physiological as well as pathological conditions, is characterized by morphological and bio- chemical features. While the importance of caspases in apoptosis is established, several noncaspase proteases (Ca2+-dependent proteases) such as calpain may play a role in the execution of apoptosis. The calpain family consists of two major isoforms, calpain I and calpain II which require ?M and mM Ca2+ con- centrations to initiate their activity. An increase in intracellular Ca2+ level is thought to trigger a cascade of biochemical processes including calpain activa- tion. Once activated, calpains degrade membrane, cytoplasmic and nuclear sub- strates, leading to the breakdown of cellular architecture and finally apoptosis. The activation of calpain has been implicated in neuronal apoptosis following spinal cord injuries and neurodegenerative diseases. This review focuses on calpain with an emphasis on its key role in the proteolysis of cellular protein substrates following apoptosis.