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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 5. min of global ischemia, while non-transgenic littermates (NTG) showed continual ATP loss. At 7. min 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 2. min and 27% higher at 5. min. 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".

Original languageEnglish (US)
Pages (from-to)236-243
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number2
DOIs
StatePublished - Aug 2011
Externally publishedYes

Fingerprint

Troponin I
Skeletal Muscle
Ischemia
Adenosine Triphosphate
Myofibrils
Glycolysis
Phenotype
Fetal Proteins
Fetal Heart
Sarcomeres
AMP-Activated Protein Kinases
Post Translational Protein Processing
Glycogen
Alanine
Lactic Acid
Phosphorylation
Costs and Cost Analysis
Glucose
Proteins

Keywords

  • Adenosine triphosphate (ATP)
  • AMP activated protein kinase (AMPK)
  • Glycolysis
  • NMR spectroscopy
  • Troponin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Pound, K. M., Arteaga, G. M., Fasano, M., Wilder, T., Fischer, S. K., Warren, C. M., ... Lewandowski, E. D. (2011). Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia. Journal of Molecular and Cellular Cardiology, 51(2), 236-243. https://doi.org/10.1016/j.yjmcc.2011.05.014

Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia. / Pound, Kayla M.; Arteaga, Grace M.; Fasano, Mathew; Wilder, Tanganyika; Fischer, Susan K.; Warren, Chad M.; Wende, Adam R.; Farjah, Mariam; Abel, E. Dale; Solaro, R. John; Lewandowski, E. Douglas.

In: Journal of Molecular and Cellular Cardiology, Vol. 51, No. 2, 08.2011, p. 236-243.

Research output: Contribution to journalArticle

Pound, KM, Arteaga, GM, Fasano, M, Wilder, T, Fischer, SK, Warren, CM, Wende, AR, Farjah, M, Abel, ED, Solaro, RJ & Lewandowski, ED 2011, 'Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia', Journal of Molecular and Cellular Cardiology, vol. 51, no. 2, pp. 236-243. https://doi.org/10.1016/j.yjmcc.2011.05.014
Pound, Kayla M. ; Arteaga, Grace M. ; Fasano, Mathew ; Wilder, Tanganyika ; Fischer, Susan K. ; Warren, Chad M. ; Wende, Adam R. ; Farjah, Mariam ; Abel, E. Dale ; Solaro, R. John ; Lewandowski, E. Douglas. / Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia. In: Journal of Molecular and Cellular Cardiology. 2011 ; Vol. 51, No. 2. pp. 236-243.
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