Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia

Kayla M Pound; Grace M Arteaga; Mathew Fasano; Tanganyika Wilder; Susan K Fischer; Chad M Warren; Adam R Wende; Mariam Farjah; E. Dale Abel; R. John Solaro; E. Douglas Lewandowski

doi:10.1016/j.yjmcc.2011.05.014

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Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia

Journal article

Peer reviewed

Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia

Kayla M Pound, Grace M Arteaga, Mathew Fasano, Tanganyika Wilder, Susan K Fischer, Chad M Warren, Adam R Wende, Mariam Farjah, E. Dale Abel, R. John Solaro, …

Journal of molecular and cellular cardiology, Vol.51(2), pp.236-243

08/2011

DOI: 10.1016/j.yjmcc.2011.05.014

PMCID: PMC3124599

PMID: 21640727

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Abstract

Changes in metabolic and myofilament phenotypes coincide in developing hearts. Posttranslational modification of sarcomere proteins influences contractility, affecting the energetic cost of contraction. However, metabolic adaptations to sarcomeric phenotypes are not well understood, particularly during pathophysiological stress. This study explored metabolic adaptations to expression of the fetal, slow skeletal muscle troponin I (ssTnI). Hearts expressing ssTnI exhibited no significant ATP loss during 5min of global ischemia, while non-transgenic littermates (NTG) showed continual ATP loss. At 7min ischemia TG-ssTnI hearts retained 80±12% of ATP versus 49±6% in NTG (P<0.05). Hearts expressing ssTnI also had increased AMPK phosphorylation. The mechanism of ATP preservation was augmented glycolysis. Glycolytic end products (lactate and alanine) were 38% higher in TG-ssTnI than NTG at 2min and 27% higher at 5min. This additional glycolysis was supported exclusively by exogenous glucose, and not glycogen. Thus, expression of a fetal myofilament protein in adult mouse hearts induced elevated anaerobic ATP production during ischemia via metabolic adaptations consistent with the resistance to hypoxia of fetal hearts. The general findings hold important relevance to both our current understanding of the association between metabolic and contractile phenotypes and the potential for invoking cardioprotective mechanisms against ischemic stress. This article is part of a Special Issue entitled "Possible Editorial". ► Isoform changes in myofilament proteins induce changes in cardiac metabolic phenotype. ► Expression of the ssTnI, in place of adult cTnI, induces metabolic protection to ischemic stress. ► Adult mouse hearts expressing ssTnI exhibit augmented glycolytic ATP production during ischemia. ► Expression of fetal ssTnI induces resistance to hypoxia, due to ischemia, similar to fetal hearts.

Glycolysis

Troponin

NMR spectroscopy

AMP activated protein kinase (AMPK)

Adenosine triphosphate (ATP)

Details

Title: Subtitle: Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia
Creators: Kayla M Pound - Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Grace M Arteaga - Program in Sarcomere Proteomics and Cardiac Dynamics, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Mathew Fasano - Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Tanganyika Wilder - Program in Sarcomere Proteomics and Cardiac Dynamics, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Susan K Fischer - Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Chad M Warren - Program in Sarcomere Proteomics and Cardiac Dynamics, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Adam R Wende - Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Mariam Farjah - Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
E. Dale Abel - Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
R. John Solaro - Program in Sarcomere Proteomics and Cardiac Dynamics, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
E. Douglas Lewandowski - Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research and Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA
Resource Type: Journal article
Publication Details: Journal of molecular and cellular cardiology, Vol.51(2), pp.236-243
DOI: 10.1016/j.yjmcc.2011.05.014
PMID: 21640727
PMCID: PMC3124599
NLM abbreviation: J Mol Cell Cardiol
ISSN: 0022-2828
eISSN: 1095-8584
Publisher: Elsevier Ltd
Language: English
Date published: 08/2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025289902771

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