Caspase-4 is partially cleaved by calpain via the impairment of Ca2+ homeostasis under the ER stress
Abstract
In the previous reports, we showed that caspase-4, which has high homology to caspase-12, plays an important role in the neural cell death via the endoplasmic reticulum (ER) stress. In addition, we elucidated the involvement of the familial Alzheimer's disease (AD)-linked presenilin-1 (PS1) mutation and beta-amyloid induced-apoptotic signaling in human neural cells in the activation (cleavage) of caspase-4. These results suggest the involvement of caspase-4 in the cell death observed in AD. To elucidate the mechanism of the cleavage of caspase-4 under ER stress, we used EGTA, a Ca(2+) chelator, because the cleavage caspase-12 has reported to be regulated by the calpain. As the results, EGTA inhibited the cleavage of caspase-4 in a concentration-dependent manner. In addition, inhibitors of calpain, which are activated by the Ca(2+), also inhibited the cleavage of caspase-4. Furthermore, EGTA and caplain inhibitors rescued the neural cell death under the ER stress. These results suggest that the disturbance of Ca(2+) homeostasis induced by ER stress should cause the activation of caspase-4 resulting in the neural cell death.
References
Citations
Related Concepts
Related Feeds
Calcium & Bioenergetics
Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.
Apoptotic Caspases
Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.