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Impaired Energy Production Contributes to Development of Failure in Taurine Deficient Heart

  • Conference paper
Taurine 10

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 975))

Abstract

Taurine forms a conjugate in the mitochondria with a uridine residue in the wobble position of tRNALeu(UUR). The resulting product, 5-taurinomethyluridine tRNALeu(UUR), increases the interaction between the UUG codon and AAU anticodon of tRNALeu(UUR), thereby improving the decoding of the UUG codon. We have shown that the protein most affected by the taurine conjugation product is ND6, which is a subunit of complex I of the respiratory chain. Thus, taurine deficiency exhibits reduced respiratory chain function. Based on these findings, we proposed that the taurine deficient heart is energy deficient. To test this idea, hearts were perfused with buffer containing acetate and glucose as substrates. The utilization of both substrates, as well as the utilization of endogenous lipids, was significantly reduced in the taurine deficient heart. This led to a 25% decrease in ATP production, an effect primarily caused by diminished aerobic metabolism and respiratory function. In addition, inefficient oxidative phosphorylation causes a further decrease in ATP generation. The data support the idea that reductions in energy metabolism, including oxidative phosphorylation, ATP generation and high energy phosphate content, contribute to the severity of the cardiomyopathy. The findings are also consistent with the hypothesis that taurine deficiency and reduced myocardial energy content increases mortality of the taurine deficient, failing heart. The clinical implications of these findings are addressed.

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References

  • Abel ED, Kaulbach HC, Tian R, Hopkins JC, Duffy J, Doetsschman T et al (1999) Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest 104:1703–1714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allo SN, Bagby L, Schaffer SW (1997) Taurine depletion, a novel mechanism for cardioprotection from regional ischemia. Am J Phys 273:H1956–H1961

    CAS  Google Scholar 

  • Campbell FM, Kozak R, Wagner A, Altarejos JY, Byck JRB, Belke DD, Severson DL, Kelly DP, Lopaschuk GD (2002) A role for peroxisome proliferator-activated receptor α (PPARα) in the control of cardiac malonyl-CoA level. J Biol Chem 277:4098–4103

    Article  CAS  PubMed  Google Scholar 

  • Coutu P, Metzger JM (2005) Genetic manipulation of calcium-handling proteins in cardiac myocytes. I. Experimental studies. Am J Physiol Heart Circ Physiol 288:H601–H612

    Article  CAS  PubMed  Google Scholar 

  • Doenst T, Pytel G, Schrepper A, Amorim P, Farber G, Shingu Y, Mohr FW, Schwarzer M (2010) Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload. Cardiovasc Res 86:461–470

    Article  CAS  PubMed  Google Scholar 

  • Fillmore N, Mori J, Lopaschuk GD (2013) Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol 171:2080–2090

    Article  Google Scholar 

  • Gaull GE (1986) Taurine as a conditionally essential nutrient in man. J Am Coll Nutr 5:121–125

    Article  CAS  PubMed  Google Scholar 

  • Hansson A, Hance N, Dufour E, Rlalntanen A, Hultenby K, Clayton DA et al (2004) A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain deficient mouse hearts. Proc Natl Acad Sci U S A 101:3136–3141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang DY, Boini KM, Lang PA, Grahammer F, Duszenko M, Heller-Stilb B, Warskulat U, Häussinger D, Lang F, Vallon V (2006) Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT. Pflugers Arch 451:668–677

    Article  CAS  PubMed  Google Scholar 

  • Ito T, Kimura Y, Uozumi Y, Takai M, Muraoka S, Matsuda T, Ueki K, Yoshiyama M, Ikawa M, Okabe M, Schaffer SW, Fujio Y, Azuma J (2008) Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol 44:927–937

    Article  CAS  PubMed  Google Scholar 

  • Ito T, Yoshikawa N, Inui T, Miyazaki N, Schaffer SW, Azuma J (2014a) Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PLoS One 2014:e107409

    Article  Google Scholar 

  • Ito T, Yoshikawa N, Schaffer SW, Azuma J (2014b) Tissue taurine depletion alters metabolic response to exercise and reduces running capacity in mice. J Amino Acids 2014:964680

    Article  PubMed  PubMed Central  Google Scholar 

  • Jong CJ, Azuma J, Schaffer S (2012) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42:2223–2232

    Article  CAS  PubMed  Google Scholar 

  • Jong CJ, Ito T, Schaffer SW (2015) The ubiquitin-proteasome system and autophagy are defective in the taurine-deficient heart. Amino Acids 47:2609–2622

    Article  CAS  PubMed  Google Scholar 

  • Jurkowska H, Niewiadomski J, Hirschberger LL, Roman HB, Mazor KM, Liu X, Locasale JW, Park E, Stipanuk MH (2016) Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo. Amino Acids 48:665–676

    Article  CAS  PubMed  Google Scholar 

  • Kaesler S, Sobiesiak M, Kneilling M, Volz T, Kempf WE, Lang PA, Lang KS, Wieder T, Heller-Stilb B, Warskulat U, Häussinger D, Lang F, Biedermann T (2012) Effective T-cell recall responses require the taurine transporter Taut. Eur J Immunol 42:831–841

    Article  CAS  PubMed  Google Scholar 

  • King KL, Stanley WC, Rosca M, Kerner J, Hoppel CL, Febbraio M (2007) Fatty acid oxidation in cardiac skeletal muscle mitochondria is unaffected by deletion of CD36. Arch Biochem Biophys 467:234–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korzeniewski B, Noma A, Matsuoka S (2005) Regulation of oxidative phosphorylation in intact mammalian heart in vivo. Biophys Chem 116:145–157

    Article  CAS  PubMed  Google Scholar 

  • Luo M, Anderson ME (2013) Mechanisms of altered Ca2+ handling in heart failure. Circ Res 113:690–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neely JR, Morgan HE (1974) Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 36:413–459

    Article  CAS  PubMed  Google Scholar 

  • Neubauer S, Horn M, Cramer M, Harre K, Newell JB, Peters W, Pabst T, Ertl G, Hahn D, Ingwall JS, Kochsiek K (1997) Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96:2190–2196

    Article  CAS  PubMed  Google Scholar 

  • Novotny MJ, Hogan PM, Paley DM, Adams HR (1991) Systolic and diastolic dysfunction of the left ventricle induced by dietary taurine deficiency in cats. Am J Phys 261:H121–H127

    CAS  Google Scholar 

  • Park E, Park SY, Dobkin C, Schuller-Levis G (2014) Development of a novel cysteine sulfinic acid decarboxylase knockout mouse: dietary taurine reduces neonatal mortality. J Amino Acids 2014:346809

    Article  PubMed  PubMed Central  Google Scholar 

  • Pion PD, Kittleson MD, Rogers QR, Morris JG (1991) Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science 237:764–768

    Article  Google Scholar 

  • Ramila KC, Jong CJ, Pastukh V, Ito T, Azuma J, Schaffer SW (2015) Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts. Am J Physiol Heart Circ Physiol 308(3):H232–H239

    Article  CAS  PubMed  Google Scholar 

  • Rascher K, Servos G, Berthold G, Hartwig HG, Warskulat U, Heller-Stilb B, Häussinger D (2004) Vis Res 44:2091–2100

    Article  CAS  PubMed  Google Scholar 

  • Schaffer S, Solodushko V, Pastukh V, Ricci C, Azuma J (2003) Possible cause of taurine-deficient cardiomyopathy: potentiation of angiotensin II action. J Cardiovasc Pharmacol 41:751–759

    Article  CAS  PubMed  Google Scholar 

  • Schaffer SW, Jong CJ, Ito T, Azuma J (2014) Role of taurine in the pathologies of MELAS and MERRF. Amino Acids 46:47–56

    Article  CAS  PubMed  Google Scholar 

  • Schaffer SW, Jong CJ, Ito T, Azuma J (2016) Impaired energy metabolism of the taurine-deficient heart. Amino Acids 48:549–558

    Article  CAS  PubMed  Google Scholar 

  • Sergeeva OA, Fleischer W, Chepkova AN, Warskulat U, Häussinger D, Siebler M, Haas HL (2007) GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition. J Physiol 585:535–548

    Article  Google Scholar 

  • Shetewy A, Shimada-Takaura K, Warner D, Jong CJ, Mehdi AB, Alexeyev M, Takahashi K, Schaffer SW (2016) Mitochondrial defects associated with β-alanine toxicity: relevance to hyper-beta-alaninemia. Mol Cell Biochem 416:11–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129

    Article  CAS  PubMed  Google Scholar 

  • Ventura-Clapier R, Garnier A, Veksler V, Joubert F (2011) Bioenergetics of the failing heart. Biochim Biophys Acta 1813:1360–1372

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of South Alabama College of Medicine, Mobile, AL, USA

    Stephen Schaffer, Chian Ju Jong, Aza Shetewy & KC Ramila

  2. School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan

    Takashi Ito

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  1. Stephen Schaffer
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  2. Chian Ju Jong
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  3. Aza Shetewy
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  4. KC Ramila
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  5. Takashi Ito
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Corresponding author

Correspondence to Stephen Schaffer .

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Editors and Affiliations

  1. Department of Life Sciences, University of Seoul, Seoul, South Korea

    Dong-Hee Lee  & Ha Won Kim  & 

  2. College of Medicine, University of South Alabama, Mobile, Alabama, USA

    Stephen W. Schaffer

  3. Department of Developmental Neurobiology, NY State Institute for Basic Research in Developmental Disabilities, New York, USA

    Eunkyue Park

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Schaffer, S., Jong, C.J., Shetewy, A., Ramila, K., Ito, T. (2017). Impaired Energy Production Contributes to Development of Failure in Taurine Deficient Heart. In: Lee, DH., Schaffer, S.W., Park, E., Kim, H.W. (eds) Taurine 10. Advances in Experimental Medicine and Biology, vol 975. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1079-2_35

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