Potential role of high molecular weight calmodulin-binding protein in cardiac injury

Ca(2+) is a major determinant of many biochemical processes in various cell types and is a critical second messenger in cell signalling. High molecular weight calmodulin-binding protein (HMWCaMBP) was originally discovered and purified in the authors' laboratory. It was identified as a homologue of calpastatin - an inhibitor of Ca(2+)-activated cysteine proteases (calpains). Decreased expression of HMWCaMBP in ischemia suggests that it is proteolyzed by calpains during ischemia and reperfusion. In normal myocardial muscle, HMWCaMBP may protect its substrate from calpains, but during an early stage of ischemia/reperfusion with increased Ca(2+) influx, calpain activity exceeds HMWCaMBP activity, leading to proteolysis of HMWCaMBP and other protein substrates, resulting in cellular damage. The role of HMWCaMBP in ischemia/reperfusion is yet to be explored. The present review summarizes developments from the authors' laboratory in the area of HMWCaMBP.