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Calpain-1-sensitive myofibrillar proteins of the human myocardium

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Abstract

Calpain-1 is a ubiquitous intracellular Ca2+-activated protease, which has been implicated in the pathogenesis of reversible myocardial depression (i.e. myocardial stunning) that follows ischemia and reperfusion via myofibrillar protein degradation. However, the target proteins of this degradative process in the human myocardium have not yet been identified. In order to compare the levels of Calpain-1 susceptibility within a set of human myofibrillar proteins (titin, α-fodrin, desmin, troponin T (cTnT), troponin I (cTnI) and α-actinin), crude left ventricular tissue homogenates were incubated for 0.5, 15, 30, 60 or 120 min in the presence of Calpain-1 (1 U or 5 U). Differences in the kinetics and extents of protein degradation were subsequently evaluated by using silver-stained SDS-polyacrylamide gels and Western immunoblot analyses. These assays revealed myofibrillar proteins with high (titin and α-fodrin), moderate (desmin and cTnT), or low (cTnI and α-actinin) relative Calpain-1 susceptibilities. The level of phosphorylation of cTnI did not explain its relatively low Calpain-1 susceptibility. Moreover, the molecular mass distributions of the truncated α-fodrin, desmin and cTnI fragments resulting from Ca2+-dependent autoproteolysis exhibited marked similarities with those of their Calpain-1-clipped products. These in vitro results shed light on a number of structural (titin, α-fodrin, desmin and α-actinin) and regulatory (cTnT and cTnI) proteins within the contractile apparatus as potential targets of Calpain-1. Their degradation may contribute to the development of postischemic stunning in the human myocardium. (Mol Cell Biochem 278: 1–8, 2005)

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Authors and Affiliations

  1. Division of Clinical Physiology, Institute of Cardiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Judit Barta, Attila Tóth, István Édes, Miklós Vaszily & Zoltán Papp

  2. Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary

    Julius Gy. Papp & András Varró

  3. Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary

    Julius Gy. Papp

Authors
  1. Judit Barta
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  2. Attila Tóth
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  3. István Édes
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  4. Miklós Vaszily
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  5. Julius Gy. Papp
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  6. András Varró
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  7. Zoltán Papp
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Barta, J., Tóth, A., Édes, I. et al. Calpain-1-sensitive myofibrillar proteins of the human myocardium. Mol Cell Biochem 278, 1–8 (2005). https://doi.org/10.1007/s11010-005-1370-7

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  • DOI: https://doi.org/10.1007/s11010-005-1370-7

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