Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis
- 14 July 2008
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 586 (14), 3537-3550
- https://doi.org/10.1113/jphysiol.2008.153577
Abstract
The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by mu-calpain proteolysis. Here we investigated the pathophysiological significance of this post-translational modification that removes amino acids 1-71 of cardiac TnT. Working heart preparations were employed to study rat acute myocardial infarction and transgenic mouse hearts over-expressing the N-terminal truncated cardiac TnT (cTnT-ND). Ex vivo myocardial infarction by ligation of the left anterior descending coronary artery induced heart failure and produced cTnT-ND not only in the infarct but also in remote zones, including the right ventricular free wall, indicating a whole organ response in the absence of systemic neurohumoral mechanisms. Left ventricular pressure overload in mouse working hearts produced increased cTnT-ND in both ventricles, suggesting a role of haemodynamic stress in triggering an acute whole organ proteolytic regulation. Transgenic mouse hearts in which the endogenous intact cardiac TnT was partially replaced by cTnT-ND showed lowered contractile velocity. When afterload increased from 55 mmHg to 90 mmHg, stroke volume decreased in the wild type but not in the transgenic mouse hearts. Correspondingly, the left ventricular rapid-ejection time of the transgenic mouse hearts was significantly longer than that of wild type hearts, especially at high afterload. The restricted deletion of the N-terminal variable region of cardiac troponin T demonstrates a novel mechanism by which the thin filament regulation adapts to sustain cardiac function under stress conditions.Keywords
This publication has 49 references indexed in Scilit:
- Differential regulation of myofilament protein isoforms underlying the contractility changes in skeletal muscle unloadingAmerican Journal of Physiology-Cell Physiology, 2007
- Shifts in the myosin heavy chain isozymes in the mouse heart result in increased energy efficiencyJournal of Molecular and Cellular Cardiology, 2007
- Selective Deletion of the NH2-Terminal Variable Region of Cardiac Troponin T in Ischemia Reperfusion by Myofibril-Associated μ-Calpain CleavageBiochemistry, 2006
- Continuous and Discontinuous Propagation in Heart MuscleJournal of Cardiovascular Electrophysiology, 2006
- Cardiac Troponin T Isoforms Affect the Ca2+Sensitivity and Inhibition of Force DevelopmentPublished by Elsevier BV ,2002
- Cyclic fluctuations in the cardiac performance of the isolated Langendorff-perfused mouse heart: pyruvate abolishes the fluctuations and has an anti-ischaemic effectActa Physiologica Scandinavica, 2002
- Exon Skipping in Cardiac Troponin T of Turkeys with Inherited Dilated CardiomyopathyJournal of Biological Chemistry, 2002
- Determination of Function in the Isolated Working Mouse Heart: Issues in Experimental DesignJournal of Molecular and Cellular Cardiology, 1998
- Complete nucleotide sequence and structural organization of rat cardiac troponin T geneJournal of Molecular Biology, 1992
- Complete nucleotide sequence of the fast skeletal troponin T geneJournal of Molecular Biology, 1986