title: Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia.
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".
authors.affiliation: 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.
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Pound
authors.forename: Grace M
authors.initials: GM
authors.lastname: Arteaga
authors.forename: Mathew
authors.initials: M
authors.lastname: Fasano
authors.forename: Tanganyika
authors.initials: T
authors.lastname: Wilder
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fischer
authors.forename: Chad M
authors.initials: CM
authors.lastname: Warren
authors.forename: Adam R
authors.initials: AR
authors.lastname: Wende
authors.forename: Mariam
authors.initials: M
authors.lastname: Farjah
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D019210:Troponin I / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019210:Troponin I; D000255:Adenosine Triphosphate; D006003:Glycogen; D055372:AMP-Activated Protein Kinases