Cardiovascular Drugs and Therapy

, Volume 26, Issue 4, pp 321–330 | Cite as

High Molecular Weight Calmodulin-Binding Protein: 20 Years Onwards—A Potential Therapeutic Calpain Inhibitor

  • Sreejit Parameswaran
  • Rajendra K. Sharma


Apoptosis in cardiovascular diseases is considered to be a major reason for heart failure. Caspase-independent apoptosis due to calpains and other proteases occurs due to increase in intracellular Ca2+ levels which act on a feed-forward mechanism. Calpains are Ca2+-activated cysteine proteases present in the cytosol as inactive proenzymes. Calpastatin is most efficient and specific calpain inhibitor present in vivo. Earlier, we had reported the expression of novel high molecular weight calmodulin-binding protein (HMWCaMBP) in human and animal cardiac tissue and in very minute quantities in brains and lungs. HMWCaMBP showed calpastatin activity and was also found to be highly homologous to calpastatin I and calpastatin II. Decreased expression of HMWCaMBP was observed during ischemia as it is susceptible to proteolysis by calpains during ischemia-reperfusion. In normal myocardium, HMWCaMBP may protect its substrate from calpains. However, during an early stage of ischemia/reperfusion due to increased Ca2+ influx, calpain activity often exceeds HMWCaMBP activity. This leads to proteolysis of HMWCaMBP and other protein substrates, resulting in cellular damage. The role of HMWCaMBP in ischemia/reperfusion is yet to be elucidated. The present review summarizes the developments in area of HMWCaMBP from the authors’ laboratory and its potential for therapy.

Key words

High molecular weight calmodulin-binding protein Calpains Ca2+ Apoptosis Ischemia Reperfusion 



High molecular weight calmodulin-binding protein




Cardiovascular diseases



The work was supported by the Heart and Stroke Foundation of Saskatchewan, Canada.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory Medicine, College of MedicineUniversity of Saskatchewan, and Cancer Research CentreSaskatoonCanada

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