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J Physiol Volume 586, Number 14, 3537-3550, July 15, 2008 DOI: 10.1113/jphysiol.2008.153577
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CARDIOVASCULAR

Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis

 Han-Zhong Feng1, Brandon J. Biesiadecki1, Zhi-Bin Yu1, M. Moazzem Hossain1 and J.-P. Jin1

1 Section of Molecular Cardiology, Evanston Northwestern Healthcare and, Northwestern University Feinberg School of Medicine, Evanston, IL 60201, USA

The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by µ-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.

(Received 5 March 2008; accepted after revision 27 May 2008; first published online 12 June 2008)
Corresponding author J.-P. Jin: Section of Molecular Cardiology, Evanston North-western Healthcare and Northwestern University Feinberg School of Medicine, Evanston, IL 60201, USA. Email: jpjin{at}northwestern.edu




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H.-Z. Feng, M. Chen, L. S. Weinstein, and J.-P. Jin
Removal of the N-terminal Extension of Cardiac Troponin I as a Functional Compensation for Impaired Myocardial {beta}-Adrenergic Signaling
J. Biol. Chem., November 28, 2008; 283(48): 33384 - 33393.
[Abstract] [Full Text] [PDF]


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