Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2003 Nov 1;375(Pt 3):753–760. doi: 10.1042/BJ20031015

Hyperthyroidism increases the uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+-ATPase.

Ana Paula Arruda 1, Wagner S Da-Silva 1, Denise P Carvalho 1, Leopoldo De Meis 1
PMCID: PMC1223713  PMID: 12887329

Abstract

The sarcoplasmic reticulum Ca2+-ATPase is able to modulate the distribution of energy released during ATP hydrolysis, so that a portion of energy is used for Ca2+ transport (coupled ATPase activity) and a portion is converted into heat (uncoupled ATPase activity). In this report it is shown that T4 administration to rabbits promotes an increase in the rates of both the uncoupled ATPase activity and heat production in sarcoplasmic reticulum vesicles, and that the degree of activation varies depending on the muscle type used. In white muscles hyperthyroidism promotes a 0.8-fold increase of the uncoupled ATPase activity and in red muscle a 4-fold increase. The yield of vesicles from hyperthyroid muscles is 3-4-fold larger than that obtained from normal muscles; thus the rate of heat production by the Ca2+-ATPase expressed in terms of g of muscle in hyperthyroidism is increased by a factor of 3.6 in white muscles and 12.0 in red muscles. The data presented suggest that the Ca2+-ATPase uncoupled activity may represent one of the heat sources that contributes to the enhanced thermogenesis noted in hyperthyroidism.

Full Text

The Full Text of this article is available as a PDF (164.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai M., Otsu K., MacLennan D. H., Alpert N. R., Periasamy M. Effect of thyroid hormone on the expression of mRNA encoding sarcoplasmic reticulum proteins. Circ Res. 1991 Aug;69(2):266–276. doi: 10.1161/01.res.69.2.266. [DOI] [PubMed] [Google Scholar]
  2. Bachman Eric S., Dhillon Harveen, Zhang Chen-Yu, Cinti Saverio, Bianco Antonio C., Kobilka Brian K., Lowell Bradford B. betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science. 2002 Aug 2;297(5582):843–845. doi: 10.1126/science.1073160. [DOI] [PubMed] [Google Scholar]
  3. Barata Hosana, de Meis Leopoldo. Uncoupled ATP hydrolysis and thermogenic activity of the sarcoplasmic reticulum Ca2+-ATPase: coupling effects of dimethyl sulfoxide and low temperature. J Biol Chem. 2002 Mar 5;277(19):16868–16872. doi: 10.1074/jbc.M200648200. [DOI] [PubMed] [Google Scholar]
  4. Boss O., Samec S., Kühne F., Bijlenga P., Assimacopoulos-Jeannet F., Seydoux J., Giacobino J. P., Muzzin P. Uncoupling protein-3 expression in rodent skeletal muscle is modulated by food intake but not by changes in environmental temperature. J Biol Chem. 1998 Jan 2;273(1):5–8. doi: 10.1074/jbc.273.1.5. [DOI] [PubMed] [Google Scholar]
  5. Cardoso Luciene C., Martins Denise C. L., Campos Denise V. B., Santos Luciana M., Corrêa da Costa Vânia M., Rosenthal Doris, Vaisman Mario, Violante Alice H. D., Carvalho Denise P. Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating activity and thyroperoxidase in toxic diffuse goiters. Eur J Endocrinol. 2002 Sep;147(3):293–298. doi: 10.1530/eje.0.1470293. [DOI] [PubMed] [Google Scholar]
  6. Chiesi M., Inesi G. The use of quench reagents for resolution of single transport cycles in sarcoplasmic reticulum. J Biol Chem. 1979 Oct 25;254(20):10370–10377. [PubMed] [Google Scholar]
  7. Clausen T., Van Hardeveld C., Everts M. E. Significance of cation transport in control of energy metabolism and thermogenesis. Physiol Rev. 1991 Jul;71(3):733–774. doi: 10.1152/physrev.1991.71.3.733. [DOI] [PubMed] [Google Scholar]
  8. Danforth E., Jr, Burger A. The role of thyroid hormones in the control of energy expenditure. Clin Endocrinol Metab. 1984 Nov;13(3):581–595. doi: 10.1016/s0300-595x(84)80039-0. [DOI] [PubMed] [Google Scholar]
  9. De Meis L. Control of heat production by the Ca2+-ATPase of rabbit and trout sarcoplasmic reticulum. Am J Physiol. 1998 Jun;274(6 Pt 1):C1738–C1744. doi: 10.1152/ajpcell.1998.274.6.C1738. [DOI] [PubMed] [Google Scholar]
  10. Dulhunty A. F., Banyard M. R., Medveczky C. J. Distribution of calcium ATPase in the sarcoplasmic reticulum of fast- and slow-twitch muscles determined with monoclonal antibodies. J Membr Biol. 1987;99(2):79–92. doi: 10.1007/BF01871228. [DOI] [PubMed] [Google Scholar]
  11. Echtay Karim S., Roussel Damien, St-Pierre Julie, Jekabsons Mika B., Cadenas Susana, Stuart Jeff A., Harper James A., Roebuck Stephen J., Morrison Alastair, Pickering Susan. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002 Jan 3;415(6867):96–99. doi: 10.1038/415096a. [DOI] [PubMed] [Google Scholar]
  12. Everts M. E., Clausen T. Effects of thyroid hormones on calcium contents and 45Ca exchange in rat skeletal muscle. Am J Physiol. 1986 Sep;251(3 Pt 1):E258–E265. doi: 10.1152/ajpendo.1986.251.3.E258. [DOI] [PubMed] [Google Scholar]
  13. Everts M. E. Effects of thyroid hormones on contractility and cation transport in skeletal muscle. Acta Physiol Scand. 1996 Mar;156(3):325–333. doi: 10.1046/j.1365-201X.1996.203000.x. [DOI] [PubMed] [Google Scholar]
  14. Fabiato A., Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75(5):463–505. [PubMed] [Google Scholar]
  15. Fitts R. H., Winder W. W., Brooke M. H., Kaiser K. K., Holloszy J. O. Contractile, biochemical, and histochemical properties of thyrotoxic rat soleus muscle. Am J Physiol. 1980 Jan;238(1):C14–C20. doi: 10.1152/ajpcell.1980.238.1.C15. [DOI] [PubMed] [Google Scholar]
  16. Fortea M. I., Soler F., Fernandez-Belda F. Insight into the uncoupling mechanism of sarcoplasmic reticulum ATPase using the phosphorylating substrate UTP. J Biol Chem. 2000 Apr 28;275(17):12521–12529. doi: 10.1074/jbc.275.17.12521. [DOI] [PubMed] [Google Scholar]
  17. Freake H. C., Oppenheimer J. H. Thermogenesis and thyroid function. Annu Rev Nutr. 1995;15:263–291. doi: 10.1146/annurev.nu.15.070195.001403. [DOI] [PubMed] [Google Scholar]
  18. Gong D. W., Monemdjou S., Gavrilova O., Leon L. R., Marcus-Samuels B., Chou C. J., Everett C., Kozak L. P., Li C., Deng C. Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. J Biol Chem. 2000 May 26;275(21):16251–16257. doi: 10.1074/jbc.M910177199. [DOI] [PubMed] [Google Scholar]
  19. Grubmeyer C., Penefsky H. S. The presence of two hydrolytic sites on beef heart mitochondrial adenosine triphosphatase. J Biol Chem. 1981 Apr 25;256(8):3718–3727. [PubMed] [Google Scholar]
  20. Hasselbach W. The reversibility of the sarcoplasmic calcium pump. Biochim Biophys Acta. 1978 Apr 10;515(1):23–53. doi: 10.1016/0304-4157(78)90007-2. [DOI] [PubMed] [Google Scholar]
  21. Inesi G. Mechanism of calcium transport. Annu Rev Physiol. 1985;47:573–601. doi: 10.1146/annurev.ph.47.030185.003041. [DOI] [PubMed] [Google Scholar]
  22. Janský L. Humoral thermogenesis and its role in maintaining energy balance. Physiol Rev. 1995 Apr;75(2):237–259. doi: 10.1152/physrev.1995.75.2.237. [DOI] [PubMed] [Google Scholar]
  23. Jiang M., Xu A., Tokmakejian S., Narayanan N. Thyroid hormone-induced overexpression of functional ryanodine receptors in the rabbit heart. Am J Physiol Heart Circ Physiol. 2000 May;278(5):H1429–H1438. doi: 10.1152/ajpheart.2000.278.5.H1429. [DOI] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Lebon V., Dufour S., Petersen K. F., Ren J., Jucker B. M., Slezak L. A., Cline G. W., Rothman D. L., Shulman G. I. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. J Clin Invest. 2001 Sep;108(5):733–737. doi: 10.1172/JCI11775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Levine J. A., Eberhardt N. L., Jensen M. D. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science. 1999 Jan 8;283(5399):212–214. doi: 10.1126/science.283.5399.212. [DOI] [PubMed] [Google Scholar]
  27. Logan-Smith M. J., Lockyer P. J., East J. M., Lee A. G. Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+. J Biol Chem. 2001 Oct 9;276(50):46905–46911. doi: 10.1074/jbc.M108778200. [DOI] [PubMed] [Google Scholar]
  28. Lowell B. B., Spiegelman B. M. Towards a molecular understanding of adaptive thermogenesis. Nature. 2000 Apr 6;404(6778):652–660. doi: 10.1038/35007527. [DOI] [PubMed] [Google Scholar]
  29. Lytton J., MacLennan D. H. Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene. J Biol Chem. 1988 Oct 15;263(29):15024–15031. [PubMed] [Google Scholar]
  30. Lytton J., Westlin M., Burk S. E., Shull G. E., MacLennan D. H. Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. J Biol Chem. 1992 Jul 15;267(20):14483–14489. [PubMed] [Google Scholar]
  31. MacLennan D. H., Brandl C. J., Korczak B., Green N. M. Amino-acid sequence of a Ca2+ + Mg2+-dependent ATPase from rabbit muscle sarcoplasmic reticulum, deduced from its complementary DNA sequence. Nature. 1985 Aug 22;316(6030):696–700. doi: 10.1038/316696a0. [DOI] [PubMed] [Google Scholar]
  32. Mitidieri F., de Meis L. Ca(2+) release and heat production by the endoplasmic reticulum Ca(2+)-ATPase of blood platelets. Effect of the platelet activating factor. J Biol Chem. 1999 Oct 1;274(40):28344–28350. doi: 10.1074/jbc.274.40.28344. [DOI] [PubMed] [Google Scholar]
  33. Nicholls D. G., Rial E. A history of the first uncoupling protein, UCP1. J Bioenerg Biomembr. 1999 Oct;31(5):399–406. doi: 10.1023/a:1005436121005. [DOI] [PubMed] [Google Scholar]
  34. Nunes M. T., Bianco A. C., Migala A., Agostini B., Hasselbach W. Thyroxine induced transformation in sarcoplasmic reticulum of rabbit soleus and psoas muscles. Z Naturforsch C. 1985 Sep-Oct;40(9-10):726–734. doi: 10.1515/znc-1985-9-1025. [DOI] [PubMed] [Google Scholar]
  36. Papa S., Skulachev V. P. Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem. 1997 Sep;174(1-2):305–319. [PubMed] [Google Scholar]
  37. Reis M., Farage M., de Souza A. C., de Meis L. Correlation between uncoupled ATP hydrolysis and heat production by the sarcoplasmic reticulum Ca2+-ATPase: coupling effect of fluoride. J Biol Chem. 2001 Sep 5;276(46):42793–42800. doi: 10.1074/jbc.M107625200. [DOI] [PubMed] [Google Scholar]
  38. Reis Marcelo, Farage Mariana, de Meis Leopoldo. Thermogenesis and energy expenditure: control of heat production by the Ca(2+)-ATPase of fast and slow muscle. Mol Membr Biol. 2002 Oct-Dec;19(4):301–310. doi: 10.1080/09687680210166217. [DOI] [PubMed] [Google Scholar]
  39. Ribeiro M. O., Carvalho S. D., Schultz J. J., Chiellini G., Scanlan T. S., Bianco A. C., Brent G. A. Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific. J Clin Invest. 2001 Jul;108(1):97–105. doi: 10.1172/JCI12584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ribeiro M. O., Lebrun F. L., Christoffolete M. A., Branco M., Crescenzi A., Carvalho S. D., Negrão N., Bianco A. C. Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat. Am J Physiol Endocrinol Metab. 2000 Aug;279(2):E314–E322. doi: 10.1152/ajpendo.2000.279.2.E314. [DOI] [PubMed] [Google Scholar]
  41. Sayen M. R., Rohrer D. K., Dillmann W. H. Thyroid hormone response of slow and fast sarcoplasmic reticulum Ca2+ ATPase mRNA in striated muscle. Mol Cell Endocrinol. 1992 Sep;87(1-3):87–93. doi: 10.1016/0303-7207(92)90236-y. [DOI] [PubMed] [Google Scholar]
  42. Silva J. E., Larsen P. R. Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature. 1983 Oct 20;305(5936):712–713. doi: 10.1038/305712a0. [DOI] [PubMed] [Google Scholar]
  43. Silva J. E. Thyroid hormone control of thermogenesis and energy balance. Thyroid. 1995 Dec;5(6):481–492. doi: 10.1089/thy.1995.5.481. [DOI] [PubMed] [Google Scholar]
  44. Simonides W. S., Brent G. A., Thelen M. H., van der Linden C. G., Larsen P. R., van Hardeveld C. Characterization of the promoter of the rat sarcoplasmic endoplasmic reticulum Ca2+-ATPase 1 gene and analysis of thyroid hormone responsiveness. J Biol Chem. 1996 Dec 13;271(50):32048–32056. doi: 10.1074/jbc.271.50.32048. [DOI] [PubMed] [Google Scholar]
  45. Simonides W. S., Thelen M. H., van der Linden C. G., Muller A., van Hardeveld C. Mechanism of thyroid-hormone regulated expression of the SERCA genes in skeletal muscle: implications for thermogenesis. Biosci Rep. 2001 Apr;21(2):139–154. doi: 10.1023/a:1013692023449. [DOI] [PubMed] [Google Scholar]
  46. Simonides W. S., van Hardeveld C. The postnatal development of sarcoplasmic reticulum Ca2+ transport activity in skeletal muscle of the rat is critically dependent on thyroid hormone. Endocrinology. 1989 Mar;124(3):1145–1152. doi: 10.1210/endo-124-3-1145. [DOI] [PubMed] [Google Scholar]
  47. Smith Wendy S., Broadbridge Robert, East J. Malcolm, Lee Anthony G. Sarcolipin uncouples hydrolysis of ATP from accumulation of Ca2+ by the Ca2+-ATPase of skeletal-muscle sarcoplasmic reticulum. Biochem J. 2002 Jan 15;361(Pt 2):277–286. doi: 10.1042/0264-6021:3610277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Soler Fernando, Fortea Maria-Isabel, Lax Antonio, Fernández-Belda Francisco. Dissecting the hydrolytic activities of sarcoplasmic reticulum ATPase in the presence of acetyl phosphate. J Biol Chem. 2002 Jul 18;277(41):38127–38132. doi: 10.1074/jbc.M203966200. [DOI] [PubMed] [Google Scholar]
  49. Sorenson M. M., Coelho H. S., Reuben J. P. Caffeine inhibition of calcium accumulation by the sarcoplasmic reticulum in mammalian skinned fibers. J Membr Biol. 1986;90(3):219–230. doi: 10.1007/BF01870128. [DOI] [PubMed] [Google Scholar]
  50. Tanford C. Twenty questions concerning the reaction cycle of the sarcoplasmic reticulum calcium pump. CRC Crit Rev Biochem. 1984;17(2):123–151. doi: 10.3109/10409238409113603. [DOI] [PubMed] [Google Scholar]
  51. Vidal-Puig A. J., Grujic D., Zhang C. Y., Hagen T., Boss O., Ido Y., Szczepanik A., Wade J., Mootha V., Cortright R. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem. 2000 May 26;275(21):16258–16266. doi: 10.1074/jbc.M910179199. [DOI] [PubMed] [Google Scholar]
  52. Wu K. D., Lee W. S., Wey J., Bungard D., Lytton J. Localization and quantification of endoplasmic reticulum Ca(2+)-ATPase isoform transcripts. Am J Physiol. 1995 Sep;269(3 Pt 1):C775–C784. doi: 10.1152/ajpcell.1995.269.3.C775. [DOI] [PubMed] [Google Scholar]
  53. Yu X., Inesi G. Variable stoichiometric efficiency of Ca2+ and Sr2+ transport by the sarcoplasmic reticulum ATPase. J Biol Chem. 1995 Mar 3;270(9):4361–4367. doi: 10.1074/jbc.270.9.4361. [DOI] [PubMed] [Google Scholar]
  54. de Lange P., Lanni A., Beneduce L., Moreno M., Lombardi A., Silvestri E., Goglia F. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology. 2001 Aug;142(8):3414–3420. doi: 10.1210/endo.142.8.8303. [DOI] [PubMed] [Google Scholar]
  55. de Meis L. Approaches to studying the mechanisms of ATP synthesis in sarcoplasmic reticulum. Methods Enzymol. 1988;157:190–206. doi: 10.1016/0076-6879(88)57075-1. [DOI] [PubMed] [Google Scholar]
  56. de Meis L., Bianconi M. L., Suzano V. A. Control of energy fluxes by the sarcoplasmic reticulum Ca2+-ATPase: ATP hydrolysis, ATP synthesis and heat production. FEBS Lett. 1997 Apr 7;406(1-2):201–204. doi: 10.1016/s0014-5793(97)00244-5. [DOI] [PubMed] [Google Scholar]
  57. de Meis L. Ca2+-ATPases (SERCA): energy transduction and heat production in transport ATPases. J Membr Biol. 2002 Jul 1;188(1):1–9. doi: 10.1007/s00232-001-0171-5. [DOI] [PubMed] [Google Scholar]
  58. de Meis L. Role of the sarcoplasmic reticulum Ca2+-ATPase on heat production and thermogenesis. Biosci Rep. 2001 Apr;21(2):113–137. doi: 10.1023/a:1013640006611. [DOI] [PubMed] [Google Scholar]
  59. de Meis L. Uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+-ATPase. Regulation by ADP. J Biol Chem. 2001 May 7;276(27):25078–25087. doi: 10.1074/jbc.M103318200. [DOI] [PubMed] [Google Scholar]
  60. de Meis L., Vianna A. L. Energy interconversion by the Ca2+-dependent ATPase of the sarcoplasmic reticulum. Annu Rev Biochem. 1979;48:275–292. doi: 10.1146/annurev.bi.48.070179.001423. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES