Role of calpains in calmodulin regulated systems

Abstract

Dysregulation of proteolytic enzymes may disrupt normal biological processes in myocardium can lead to various cardiac conditions. Substantial evidence supports the involvement of matrix metalloproteinase, cystine and serine protease families in this process. Calpain is an intracellular Ca 2+ -activated protease. Deregulation of calpain caused by a disruption of calcium homeostasis during cardiac pathologies such as atrial fi brillation, heart failure, hypertrophy, or ischemia reperfusion, and thus the myocardial damage. Calpain-calcineurin signalling is pivotal in cardiac conditions especially ischemia, since the signalling produces a cascading effect on the outcome of ischemia. The cleavage of phosphodiesterase1 by calpain is crucial for the regulation of cyclic nucleotides especially cAMP and cGMP. Turnover of cAMP and cGMP in cardiac tissue determines how the cells respond and survive to ischemic insult. Among the known calpain inhibitors, the most specifi c and potent inhibitor is calpastatin, which belongs to the calpain family. Further research on calpain structures will help in determining the conditions required for activation and the ability of calpain specifi cally proteolyse even untagged substrates. Though many interesting reviews have covered on the entire calpain system, the current manuscript focuses on the research carried out on calpains in relation to cardiac system by describing their interaction with 2 important cardiac specific proteins-calcineurin and phosphodiesterase 1.