Calpain-1-sensitive myofibrillar proteins of the human myocardium

Judit Barta, Attila Tóth, I. Édes, Miklós Vaszily, J. Papp, A. Varró, Z. Papp

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume278
Issue number1-2
DOIs
Publication statusPublished - Oct 2005

Fingerprint

Calpain
Myocardium
Troponin I
Desmin
Connectin
Actinin
Proteins
Degradation
Proteolysis
Myocardial Stunning
Contractile Proteins
Troponin T
Phosphorylation
Molecular mass
Silver
Reperfusion
Assays
Ischemia
Western Blotting
Tissue

Keywords

  • α-actinin
  • α-fodrin
  • Calpain
  • Desmin
  • Stunning
  • Titin
  • Troponin I
  • Troponin T

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Calpain-1-sensitive myofibrillar proteins of the human myocardium. / Barta, Judit; Tóth, Attila; Édes, I.; Vaszily, Miklós; Papp, J.; Varró, A.; Papp, Z.

In: Molecular and Cellular Biochemistry, Vol. 278, No. 1-2, 10.2005, p. 1-8.

Research output: Contribution to journalArticle

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