Research article summary (published 10 Jun 2008):

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

Full 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.

Author information

Author/s: Feng, Han-Zhong (HZ); Biesiadecki, Brandon J (BJ); Yu, Zhi-Bin (ZB); Hossain, M Moazzem (MM); Jin, J-P (JP);

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

Grants: AR-048816 (Agency:NIAMS NIH HHS) ; HL-078773 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of physiology (J Physiol), published in England. (Language: eng)

Reference: 2008-Jul; vol 586 (issue 14) : pp 3537-50

Dates: Created 2008/07/15; Completed 2008/10/27; Revised 2009/07/16;

PMID: 18556368, status: MEDLINE (last retrieval date: 7/25/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adaptation, Physiological Animals Energy Metabolism - physiology Gene Expression Regulation - physiology Heart - drug effects Mice Mice, Transgenic Myocardial Infarction

Myocardial Infarction Myocardium - metabolism Protein Processing, Post-Translational Rats Rats, Sprague-Dawley Reperfusion Injury Stress, Mechanical Troponin T - genetics; metabolism

Associated Chemicals: Troponin T (0)

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