Thyroid hormones and the creatine kinase system in cardiac cells

  • Enn K. Seppet
  • Valdur A. Saks
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 13)

Abstract

The paper reviews the current evidence on the role of thyroid hormones in regulating the creatine kinase energy transfer system at multiple structures in cardiac cells. 1) Thyroid hormones modulate the overall synthesis of phosphocreatine (PCr) by increasing the rate of mitochondrial oxidative phosphorylation. 2) Thyroid hormones regulate the total activity of creatine kinase and its isoenzyme distribution. In comparison with normal thyroid state (euthyroidism), hypothyroidism is characterized by decreased total creatine kinase activity owing to diminished fraction of creatine kinase. On the other hand, hyperthyroidism, while causing no change in total creatine kinase activity, leads to increased fractions of neonatal isoforms of creatine kinase, and, in case of prolonged hyperthyroidism, to decreased fraction of mitochondrial creatine kinase. The latter change is associated with partial uncoupling between mitochondrial creatine kinase and adenine nucleotide translocase reflected by decreased PCr/O ratio. 3) Hyperthyroidism leads to increased passive sarcolemmal permeability due to which the leakage of creatine along its concentration gradient occurs. As a result of (i) increased sarcolemmal permeability for creatine, (ii) uncoupling of mitochondrial PCr synthesis, and (iii) increased energy utilization rate the steady state intracellular PCr content decreases under hyperthyroidism which, in turn, increases the myocardial susceptibility to hypoxic damage. Thyroid state also modulates the protective effects of exogenous PCr on energetically depleted myocardium. (Mol Cell Biochem 133/134: 299–309, 1994)

Key words

hypothyroidism hyperthyroidism oxidative phosphorylation phosphocreatine synthesis creatine kinase isoenzymes creatine transport intracellular energy transfer myocardium 

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References

  1. 1.
    Skelton CL, Pool PE, Seagren SC, Braunwald E: Mechanochemistry of cardiac muscle. V. Influence of thyroid state on energy utilization. J Clin Invest 50: 463–473, 1971Google Scholar
  2. 2.
    Morkin E, Flink IL, Goldman S: Biochemical and physiological effects of thyroid hormone on cardiac performance. Progress Cardiovasc Dis 25: 435–463, 1983CrossRefGoogle Scholar
  3. 3.
    Philipson KD, Edelman JS: Thyroid hormone control of Na+-K+-ATPase and K+ dependent phosphatase in rat heart. Am J Physiol 232: C196–C201, 1977PubMedGoogle Scholar
  4. 4.
    Horowitz B, Hensley CB, Quintero M, Azuma KK, Putnam D, McDonough AA: Differential regulation of Na,K-ATPase 1, 2, and subunit mRNA and protein levels by thyroid hormone. J Biol Chem 265: 14308–14314, 1990PubMedGoogle Scholar
  5. 5.
    Daly MJ, Seppet EK, Vetter R, Dhalla NS: Membrane abnormalities and changes in cardiac cations due to alterations in thyroid status. In: B Korecky, NS Dhalla (eds) Subcellular Basis of Contractile Failure. Boston, Kluwer Academic Publishers, pp 173–191, 1990CrossRefGoogle Scholar
  6. 6.
    Suko J: The calcium pump of cardiac sarcoplasmic reticulum. Functional alterations of different levels of thyroid state in rabbits. J Physiol 228: 563–581, 1973PubMedCentralPubMedGoogle Scholar
  7. 7.
    Limas CJ: Calcium transport ATPase of cardiac sarcoplasmic reticulum in experimental hyperthyroidism. Am J Physiol 235: H745–H751, 1978PubMedGoogle Scholar
  8. 8.
    Dillmann WH: Biochemical basis of thyroid hormone action in the heart. Am J Med 88: 626–630, 1990PubMedCrossRefGoogle Scholar
  9. 9.
    Piatnek-Leunissen DA, Leunissen RLA: Heart mitochondrial function in acute and chronic hyperthyroidism in rats. Circ Res 25: 171–181, 1969PubMedCrossRefGoogle Scholar
  10. 10.
    Read LC, Wallace PG, Berry MN: Effects of thyroid state on respiration of perfused rat and guinea pig hearts. Am J Physiol 253: H519–H523, 1987PubMedGoogle Scholar
  11. 11.
    Nishiki K, Erecinska M, Wilson DF, Cooper S: Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid and hyperthyroid rats. Am J Physiol 235: C212–C219, 1988Google Scholar
  12. 12.
    Seppet EK, Kadaya LY, Kallikorm AP, Saks VA: Hormone regulation of cardiac energy metabolism. II. The effect of thyroid state on the coupling between the reactions of oxidative phosphorylation and phosphocreatine synthesis in rat heart mitochondria. J Appl Cardiol 5: 367–381, 1990Google Scholar
  13. 13.
    Seymour A-M L, Eldar H, Radda GK: Hyperthyroidism results in increased glycolytic capacity in the rat heart. A. 31P-NMR study. Biochim Biophys Acta 1055: 107–116, 1990PubMedCrossRefGoogle Scholar
  14. 14.
    Seppet EK, Kadaya LY, Hata T, Kallikorm AP, Saks VA, Vetter R, Dhalla NS: Thyroid control over membrane processes in rat heart. Am J Physiol, Suppl (Oct) 26: 66–71, 1991Google Scholar
  15. 15.
    Fitch CD, Shields RP: Creatine metabolism in skeletal muscle. I. Creatine movement across muscle membranes. J Biol Chem 241: 3611–3614, 1966PubMedGoogle Scholar
  16. 16.
    Fitch CD, Shields RP, Payne WF, Dacus JM: Creatine metabolism in skeletal muscle. III. Specificity of the creatine entry process. J Biol Chem 243: 2024–2027, 1968PubMedGoogle Scholar
  17. 17.
    Seppet EK, Adoyaan AJ, Kallikorm AP, Chernousova GB, Lyulina NV, Sharov VG, Severin VV, Popovich MI, Saks VA: Hormone regulation of cardiac energy metabolism. I. Creatine transport across cell membranes of euthyroid and hyperthyroid rat heart. Biochem Med 34: 267–279, 1985PubMedCrossRefGoogle Scholar
  18. 18.
    Syllm-Rapoport I: Creatine transport into human red blood cells. Acta Biol Med Ger 36: 3–4, 1977Google Scholar
  19. 19.
    Bodansky MJ: Effect of thyroid and thyroxine on concentration of creatine in heart, muscle, liver and testes of albino rat. J Biol Chem 109: 615–622, 1935Google Scholar
  20. 20.
    Buccino RA, Spann JF Jr, Pool PE, Sonnenblick EH, Braunwald E: Influence of the thyroid state on the intrinsic contractile properties and energy stores of the myocardium. J Clin Invest 46: 1669–1682, 1967PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Kurahashi M: Tissue specificity of inhibitory action of excess thyroid hormone on creatine transport in the rat. Japan J Physiol 28: 603–610, 1978CrossRefGoogle Scholar
  22. 22.
    Fitch CD, Coker R, Dinning JS: Metabolism of creatine-l-C14 by vitamin E-deficient and hyperthyroid rats. Am J Physiol 198: 1232–1234, 1960PubMedGoogle Scholar
  23. 23.
    Kessler-Icekson G: Effect of triiodothyronine on cultured neonatal rat heart cells: beating rate, myosin subunits and CK-isozymes. J Mol Cell Cardiol 20: 649–655, 1988PubMedCrossRefGoogle Scholar
  24. 24.
    Brik H, Alkaslassi L, Harell D, Sperling O, Shainberg A: Thyroxine-induced redistribution of creatine kinase isoenzymes in rat cardiomyocytes cultures. Experientia 45: 592–594, 1989Google Scholar
  25. 25.
    Schyler GT, Yarbrough LR: Comparison of myosin and creatine kinase isoforms in left ventricles of young and senescent Fischer 344 rats after treatment with triiodothyronine. Mech Ageing Dev 56: 39–48, 1990CrossRefGoogle Scholar
  26. 26.
    Schyler GT, Yarbrough LR: Changes in myosin and creatine kinase mRNA levels with cardiac hypertrophy and hypothyroidism. Basic Res Cardiol 85: 481–494, 1990CrossRefGoogle Scholar
  27. 27.
    Seppet EK, Kairane CB, Khuchua ZA, Kadaya LY, Kallikorm AP, Saks VA: Hormone regulation of cardiac energy metabolism. III. Effect of thyroid state on distribution of creatine kinase isoenzymes and creatine-controlled respiration in cardiac muscle. J Appl Cardiol 6: 301–311, 1991Google Scholar
  28. 28.
    Saks VA, Rosenstraukh LV, Smirnov VN, Chazov EI: Role of creatine phosphokinase in cellular function and metabolism. Can J Physiol Pharmacol 56: 691–706, 1978PubMedCrossRefGoogle Scholar
  29. 29.
    Younes A, Schneider JM, Bercovici J, Swynghedauw B: Redistribution of creatine kinase isoenzymes in chronically overloaded myocardium. Cardiovasc Res 19: 15–19, 1984CrossRefGoogle Scholar
  30. 30.
    Smith SH, Kramer MF, Reis I, Bishop SP, Ingwall JS: Regional changes in creatine kinase and myocyte size in hypertensive and nonhypertensive cardiac hypertrophy. Circ Res 67: 1334–1344, 1990PubMedCrossRefGoogle Scholar
  31. 31.
    Veksler VV, Kuznetsov AV, Sharov VG, Kapelko VG, Saks VA: Mitochondrial respiratory parameters in cardiac tissue: a novel method for assessment by using saponin-skinned fibers. Biochim Biophys Acta 892: 191–196, 1987PubMedCrossRefGoogle Scholar
  32. 32.
    Simonides WS, van Hardeveld C: The postnatal development of sarcoplasmic reticulum Ca2+ activity in skeletal muscle of the rat is critically dependent on thyroid hormone. Endocrinology 124: 1145–1153, 1989PubMedCrossRefGoogle Scholar
  33. 33.
    Soboll S: Thyroid hormone action on mitochondrial energy transfer. Biochim Biophys Acta 1144: 1–16, 1993PubMedCrossRefGoogle Scholar
  34. 34.
    Bronk JR: Thyroid hormones: control of terminal oxidation. Science 141: 816–818, 1963PubMedCrossRefGoogle Scholar
  35. 35.
    Shears SB, Bronk JR: The influence of thyroxine administered in vivo on the transmembrane protonic electrochemical potential difference in rat liver mitochondria. Biochem J 178: 505–507, 1979PubMedCentralPubMedGoogle Scholar
  36. 36.
    Horrum MA, Tobin RB, Ecklund RE: Thyroxine-induced changes in rat liver mitochondrial cytochromes. Mol Cell Endocrinol 41: 163–169, 1985PubMedCrossRefGoogle Scholar
  37. 37.
    Verhoven AJ, Kamer P, Groen AK, Tager JM: Effects of thyroid hormone on mitochondrial oxidative phosphorylation. Biochem J 226: 183–192, 1985Google Scholar
  38. 38.
    Hoch FL: Early action of injected L-thyroxine on mitochondrial oxidative phosphorylation. Proc Natl Acad Sci USA 58: 506–512, 1967PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Sterling K, Brenner MA, Sakurada T: Rapid effect of triiodothyronine on the mitochondrial pathway in rat liver in vivo. Science 210: 340–342, 1980PubMedCrossRefGoogle Scholar
  40. 40.
    Palacios-Romero R, Mowbray J: Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3’-tri-iodo-thyronine in rats. Biochem J 184: 527–538, 1979PubMedCentralPubMedGoogle Scholar
  41. 41.
    Keogh JM, Matthews PM, Seymour AM, Radda GK: A phosphorus-31-nuclear magnetic resonance study of effects of altered thyroid state on cardiac bioenergetics. Adv Myocardiol 6: 299–309, 1985PubMedGoogle Scholar
  42. 42.
    Crespo-Armas A, Mowbray J: The rapid alteration by tri-iodo Lthyronine in vivo of both the ADP/O ratio and H+/0 ratio in hypothyroid-rat liver mitochondria. Biochem J 241: 657–661, 1987PubMedCentralPubMedGoogle Scholar
  43. 43.
    Hafner RP, Brand MD: Hypothyroidism in rats does not lower mitochondrial ADP/O and H+/O ratios. Biochem J 250: 477–484, 1988PubMedCentralPubMedGoogle Scholar
  44. 44.
    Corrigall J, Tselentis BS, Mowbray J: The efficiency of oxidative phosphorylation and the rapid control by thyroid hormone of nicotinamide nucleotide reduction and transhydrogenation in intact rat liver mitochondria. Eur J Biochem 141: 435–440, 1984PubMedCrossRefGoogle Scholar
  45. 45.
    Thomas WE, Crespo-Armas A, Mowbray J: The influence of nanomolar calcium ions and physiological levels of thyroid hormone on oxidative phosphorylation in rat liver mitochondria. A possible signal amplification control mechanism. Biochem J 247: 315–320, 1987Google Scholar
  46. 46.
    Thomas WE, Mowbray J: Evidence for ADP-ribosylation in the mechanism of rapid thyroid hormone control of mitochondria. FEBS Lett 223: 279–283, 1987PubMedCrossRefGoogle Scholar
  47. 47.
    Groen AK, Wanders RJA, Westerhoff HV, Van der Meer R, Tager JM: Quantification of the contribution of various steps to the control of mitochondrial respiration. J Biol Chem 257: 2754–2757, 1982PubMedGoogle Scholar
  48. 48.
    Shears SB, Bronk JR: Ion transport in liver mitochondria from normal and thyroxine-treated rats. J Bioenerg Biomembr 12: 379–393, 1980PubMedCrossRefGoogle Scholar
  49. 49.
    Babior BM, Creagan S, Ingbar S, Kipnes RS: Stimulation of mitochondrial adenosine diphosphate uptake by thyroid hormones. Proc Nat Acad Sci USA 70: 98–102, 1973PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Mowbray J, Corrigall J: Short-term control of mitochondrial adenine nucleotide translocator by thyroid hormone. Eur J Biochem 139: 95–99, 1984PubMedCrossRefGoogle Scholar
  51. 51.
    Das AM, Harris DA: Control of mitochondrial ATP synthase in rat cardiomyocytes: effects of thyroid hormone. Biochim Biophys Acta 1096: 294–290, 1991Google Scholar
  52. 52.
    Tanaka T, Morita H, Koide H, Kawamura K, Takatsu T: Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat myocardium. Bas Res Cardiol 80: 165–174, 1985CrossRefGoogle Scholar
  53. 53.
    Bronk JR: Thyroid hormone: effects on electron transport. Science 153: 638–639, 1966PubMedCrossRefGoogle Scholar
  54. 54.
    Volfin P, Kaplay SS, Sanadi DR: Early effect of thyroxine in vivo on rapidly labeled mitochondrial protein fractions and respiratory control. J Biol Chem 244: 5631–5635, 1969PubMedGoogle Scholar
  55. 55.
    Katyare SS, Joshi MV, Fatterpaker P, Sreenivasan A: Effect of thyroid deficiency on oxidative phosphorylation in rat liver, kidney, and brain mitochondria. Arch Biochem Biophys 182: 155–163, 1977PubMedCrossRefGoogle Scholar
  56. 56.
    Hoch FL: Thyroid control over biomembranes. VII. Heart muscle mitochondria from L-triiodothyronine-injected rats. J Mol Cell Cardiol 14: 81–90, 1982Google Scholar
  57. 57.
    Muller MJ, Seitz HJ: Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo-and hyperthyroidism. Clin Wochenschr 62: 49–55, 1984CrossRefGoogle Scholar
  58. 58.
    Paradies G, Ruggiero FM: Effect of hyperthyroidism on the transport of pyruvate in rat-heart mitochondria. Biochim Biophys Acta 935: 79–86, 1988PubMedCrossRefGoogle Scholar
  59. 59.
    Paradies G, Ruggiero FM: Enhanced activity of the tricarboxylate carrier and modification of lipids in hepatic mitochondria from hyperthyroid rats. Arch Biochem Biophys 278: 425–430, 1990PubMedCrossRefGoogle Scholar
  60. 60.
    Hoch FL: Adenine nucleotide translocation in liver mitochondria of hypothyroid rats. Arch Biochem Biophys 178: 535–545, 1977PubMedCrossRefGoogle Scholar
  61. 61.
    Sterling K: The molecular mechanism of thyroid hormone action at the cellular level. In: LC van Middlesworth (ed) The Thyroid Gland: Practical Clinical Treatise. Year Book, Chicago, pp 203–229, 1986Google Scholar
  62. 62.
    Sterling K, Milch PO, Brenner MA, Lazarus JH: Thyroid hormone action: The mitochondrial pathway. Science 197: 996–999, 1977PubMedCrossRefGoogle Scholar
  63. 63.
    Mutvei A, Husman B, Andersson G, Nelson BD: Thyroid hormone and not growth hormone is the principle regulator of mammalian mitochondrial biogenesis. Acta Endocrinol (Copenh) 121: 223–228,1989Google Scholar
  64. 64.
    Leung ACF, McKee EE: Mitochondrial protein synthesis during thyroxine-induced cardiac hypertrophy. Am J Physiol 258: E511–E518, 1990PubMedGoogle Scholar
  65. 65.
    Winder WW, Holloszy JO: Response of mitochondria of different types of skeletal muscle to thyrotoxicosis. Am J Physiol 232: C180–C184, 1977PubMedGoogle Scholar
  66. 66.
    Saks VA, Kupriyanov VV, Elizarova G, Jacobus WE: Studies of energy transport in heart cells. The importance of creatine kinase localization for the coupling of mitochondrial phosphorylcreatine production to oxidative phosphorylation. J Biol Chem 255: 755–763, 1980PubMedGoogle Scholar
  67. 67.
    Wyss M, Smeitink J, Wevers RA, Wallimann T: Mitochondrial creatine kinase: a key enzyme to aerobic energy metabolism. Biochim Biophys Acta 1102: 119–166, 1992PubMedCrossRefGoogle Scholar
  68. 68.
    Saks VA, Kuznetsov AV, Huchua ZA, Kupriyanov VV: Compartmentation of adenine nucleotides and phosphocreatine shuttle in cardiac cells: some new evidence. Adv Exp Med Biol 194: 103–116, 1986PubMedCrossRefGoogle Scholar
  69. 69.
    Kupriyanov VV, Elizarova GV, Saks VA: Determination of the molar content of creatine kinase in heart mitochondria using SHreagents. Biokhimia 46: 930–941, 1981 (In Russian)Google Scholar
  70. 70.
    Palacios J, Kiran S, Powell WJ: Effect of hypoxia on mechanical properties of hyperthyroid cat papillary muscle. Am J Physiol 237: H293–H298, 1979PubMedGoogle Scholar
  71. 71.
    Hearse DJ, Garlick PB, Humphrey SM: Ischemic contracture of the myocardium: mechanisms and prevention. Am J Cardiol 39: 986–993, 1977PubMedCrossRefGoogle Scholar
  72. 72.
    Ventura-Clapier R, Vassort G: Electrical and mechanical activities of frog heart during energetic deficiency. J Muscle Res Cell Motil 1: 429–444, 1980CrossRefGoogle Scholar
  73. 73.
    Reilly PJ, Cooksey JD: Cardiac energy stores and creatine in experimental cardiac hypertrophy. Proc Soc Exp Biol Med 161: 193–198, 1979PubMedCrossRefGoogle Scholar
  74. 74.
    Khuchua ZA, Ventura-Clapier R, Kuznetsov AV, Grishin MN, Saks VA: Alterations in the creatine kinase system in the myocardium of cardiomyopathic hamsters. Biochem Biophys Res Commun 165: 748–757, 1989PubMedCrossRefGoogle Scholar
  75. 75.
    Ingwall JS, Fossel ET: Changes in the creatine kinase system in the hypertrophied myocardium of the dog and rat. In: NR Alpert (ed) Myocardial Hypertrophy and Failure. Persp Cardiovasc Res, Vol 7, pp 601–617. Raven Press, New York, 1983Google Scholar
  76. 76.
    Rosenstraukh LV, Saks VA, Undrovinas AI, Chazov EI, Smirnov VN, Sharov VG: Studies of energy transport in heart cells. The effect of creatine phosphate on the frog ventricular contractile force and action potential duration. Biochem Med 19: 148–164, 1978CrossRefGoogle Scholar
  77. 77.
    Hearse DJ, Stewart DA, Braimbridge MV: Cellular protection during myocardial ischemia. The development and characterization of a procedure for the induction of reversible ischemic arrest. Circulation 54: 193–202, 1976PubMedCrossRefGoogle Scholar
  78. 78.
    Fagbemy O, Kane KA, Parratt JR: Creatine phosphate suppresses ventricular arrhythmias resulting from coronary artery ligation. J Cardiovasc Pharmacol 4: 53–58, 1982CrossRefGoogle Scholar
  79. 79.
    Saks VA, Javadov SA, Pozin E, Preobrazhensky AN: Biochemical basis of the protective action of phosphocreatine on the ischemic myocardium. In: VA Saks, YG Bobkov, E Strumia (eds) Creatine Phosphate, Biochemistry, Pharmacology and Clinical Efficiency. Edizioni Minerva Medica, Torino, pp 95–111, 1987Google Scholar
  80. 80.
    Seppet EK, Eimre MA, Kallikorm AP, Saks VA: Effect of exogenous phosphocreatine on heart muscle contractility modulated by hyperthyroidism and extracellular calcium concentration. J Appl Cardiol 3: 369–380, 1988Google Scholar
  81. 81.
    Sharov VG, Javadov SA, Beskrovnova NN, Tolokolnikov AV, Kryzhanovsky SA, Kaverina NV, Bobkov YG: Ultrastructural aspects of protective effect of exogenous phosphocreatine on ischemic myocardium. In: VA Saks, YG Bobkov, E Strumia (eds) Creatine Phosphate, Biochemistry, Pharmacology and Clinical Efficiency. Edizioni Minerva Medica, Torino, pp 112–122, 1987Google Scholar
  82. 82.
    Anukhovsky EP, Javadov SA, Preobrazhensky AN, Beloshapko GG, Rosenstraukh LV, Saks VA: Effect of phosphocreatine and related compounds on the phospholipid metabolism of ischemic heart. Biochem Med Metab Biol 35: 327–334, 1986CrossRefGoogle Scholar
  83. 83.
    Javadov SA, Preobrazhensky AN, Saks VA: Action of phosphocreatine on lysophosphoglyceride levels under total ischemia in rat myocardium. Biokhimia 51: 668–674, 1986Google Scholar
  84. 84.
    Breccia A, Fini A, Girotti S: Intracellular distribution of doublelabelled creatine phosphate in the rabbit myocardium. Curr Ther Res 37: 1205–1215, 1985Google Scholar
  85. 85.
    Preobrazhensky AN, Javadov SA, Saks VA: Study on the mechanisms of the protective action of phosphocreatine on the ischemic myocardium. Biokhimia 51: 675–683, 1986Google Scholar
  86. 86.
    Ruigrok TJC, Boink ARTJ, Spies F, Blok J, Maas AHJ, Zimmermann ANE: Energy dependency of the calcium paradox. J Mol Cell Cardiol 10: 991–1002, 1978PubMedCrossRefGoogle Scholar
  87. 87.
    Brierley GP, Murer E, Bachmann E: Studies on ion transport. III. The accumulation of calcium and inorganic phosphate by heart mitochondria. Arch Biochem Biophys 105: 89–102, 1964Google Scholar
  88. 88.
    Ganote CE, Nayler WG: Contracture and calcium paradox. J Mol Cell Cardiol 17: 733–745,1985PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1994

Authors and Affiliations

  • Enn K. Seppet
    • 1
  • Valdur A. Saks
    • 2
  1. 1.Department of Pathophysiology, Medical FacultyUniversity of TartuTartuEstonia
  2. 2.Laboratory of BioenergeticsInstitute of Chemical and Biological PhysicsTallinnEstonia

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