Role of High Molecular Weight Calmodulin Binding Protein in Cardiac Muscle

Abstract

High molecular weight calmodulin binding protein (HMWCaMBP) was originally discovered and purified in our laboratory and identified as a homologue of the calpains inhibitor, calpastatin. Calpains are Ca2+-dependent cysteine proteases that regulate various enzymes, transcription factors and structural proteins through limited proteolysis. Decreased expression of HMWCaMBP in ischemia suggests that it may be susceptible to proteolysis by calpains during ischemia and reperfusion. HMWCaMBP may protect its substrates from calpains in the normal myocardium, however during an early phase of ischemia and reperfusion with increased Ca2+ influx calpain activity exceeds HMWCaMBP activity leading to its proteolysis and of other substrates resulting in cellular injury. This study will lead to a better understanding of the pathology of disease states and the development of novel therapeutics. The exact role of HMWCaMBP in ischemia and reperfusion is not clear because most of the studies have been carried out in vitro. Therefore, it is essential that further research should be directed to in vivo studies. The nucleic acid and amino acid sequence information of HMWCaMBP will help us to do further characterization of this protein.