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Effect of thyroid hormone on Mg2+ homeostasis and extrusion in cardiac cells

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Abstract

The present study investigated the effect of alteration in thyroid hormone level on Mg2+ homeostasis in cardiac ventricular myocytes. Hyperthyroid conditions increased cardiac myocytes total Mg2+ content by ~14% as compared to cells from eu-thyroid animals. The excess Mg2+ was localized predominantly within cytoplasm and mitochondria, and was mobilized into the extracellular compartment by addition of isoproterenol (ISO) or cAMP but not phenylephrine (PHE). Hypothyroid conditions, instead, decreased cardiac myocytes total Mg2+ content by ~10% as compared to cells from eu-thyroid animals. Also in this case, cytoplasm and mitochondria were the two cellular pools predominantly affected. Under hypothyroid conditions, administration of ISO or cAMP resulted in a decreased Mg2+ extrusion as compared to that observed in cardiac cells from eu-thyroid animals. Similar changes in cellular Mg2+ content and transport were observed in cardiac ventricular myocytes isolated from hyper- and hypo-thyroid animals, as well as in cultures of H9C2 cells rendered hyper- or hypo-thyroid under in vitro conditions. Supplementation of thyroid hormone to hypothyroid animals restored Mg2+ level and transport to levels comparable to those observed in eu-thyroid animals. Taken together, these results indicate that changes in thyroid hormone level have a major effect on Mg2+ homeostasis and compartmentation in cardiac cells. The enlarged Mg2+ mobilization via β- but not α1-adrenergic receptor stimulation further suggests that β- and α1-adrenergic receptors target selectively different Mg2+ compartments within the cardiac myocyte. These results provide a new rationale to interpret changes in cardiac function under hyper- or hypo-thyroid conditions.

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Abbreviations

EPXMA:

Electron probe X-rays microanalysis

FCCP:

Carbonyl cyanide p-trifluoromethoxy-phenylhydrazone

ISO:

Isoproterenol

PHE:

Phenylephrine

H+H:

Hypo-thyroid + hyper-T3 treatment

References

  1. Gunther T (1986) Functional compartmentation of intracellular magnesium. Magnesium 5:53–59

    PubMed  CAS  Google Scholar 

  2. Romani A, Scarpa A (2000) Regulation of cellular magnesium. Front Biosci 5:D720–D734. doi:10.2741/Romani

    Article  PubMed  CAS  Google Scholar 

  3. Wolf FI, Torsello A, Fasanella S, Cittadini A (2003) Cell Physiology of magnesium. Mol Asp Med 24:11–26. doi:10.1016/S0098-2997(02)00088-2

    Article  CAS  Google Scholar 

  4. Scarpa A, Brinley FJ (1981) In situ measurements of free cytosolic magnesium ions. Fed Proc 40:2646–2652

    PubMed  CAS  Google Scholar 

  5. Fatholahi M, LaNoue K, Romani A, Scarpa A (2000) Relationship between total and free cellular Mg2+ during metabolic stimulation of rat cardiac myocytes and perfused hearts. Arch Biochem Biophys 374:395–401. doi:10.1006/abbi.1999.1619

    Article  PubMed  CAS  Google Scholar 

  6. Romani A, Scarpa A (1990) Hormonal control of Mg2+ transport in the heart. Nature 346:841–844. doi:10.1038/346841a0

    Article  PubMed  CAS  Google Scholar 

  7. Vormann J, Gunther T (1987) Amiloride-sensitive net Mg2+ efflux from isolated perfused rat hearts. Magnesium 6:220–224

    PubMed  CAS  Google Scholar 

  8. Romani A, Scarpa A (1990) Norepinephrine evokes a marked Mg2+ efflux from liver cells. FEBS Lett 269:37–40. doi:10.1016/0014-5793(90)81113-3

    Article  PubMed  CAS  Google Scholar 

  9. Fagan TE, Romani A (2000) Activation of Na+- and Ca2+-dependent Mg2+ extrusion by alpha1- and beta-adrenergic agonists in rat liver cells. Am J Physiol 279:G943–G950

    CAS  Google Scholar 

  10. Wolf FI, Di Francesco A, Covacci V, Cittadini A (1997) Regulation of magnesium efflux from rat spleen lymphocytes. Arch Biochem Biophys 344:397–403. doi:10.1006/abbi.1997.0199

    Article  PubMed  CAS  Google Scholar 

  11. Flatman PW (1991) Mechanisms of magnesium transport. Annu Rev Physiol 53:259–271. doi:10.1146/annurev.ph.53.030191.001355

    Article  PubMed  CAS  Google Scholar 

  12. Resnick LM, Altura BT, Gupta RK, Laragh JH, Alderman MH, Altura BM (1993) Intracellular and extracellular magnesium depletion in type-II (non-insulin-dependent) diabetes mellitus. Diabetologia 36:767–770. doi:10.1007/BF00401149

    Article  PubMed  CAS  Google Scholar 

  13. Wallach S, Verch R (1987) Tissue magnesium content in diabetic rats. Magnesium 6:302–307

    PubMed  CAS  Google Scholar 

  14. Runyan AL, Sun Y, Bhattacharya SK, Ahokas RA, Chhokar VS, Gerling IC et al (2005) Responses in extracellular and intracellular calcium and magnesium in aldosteronism. J Lab Clin Med 146:76–84. doi:10.1016/j.lab.2005.04.008

    Article  PubMed  CAS  Google Scholar 

  15. Sontia B, Touyz RM (2007) Role of magnesium in hypertension. Arch Biochem Biophys 458:33–39. doi:10.1016/j.abb.2006.05.005

    Article  PubMed  CAS  Google Scholar 

  16. Kahaly GS, Dillmann WH (2005) Thyroid hormone action in the heart. Endocr Rev 26:704–728. doi:10.1210/er.2003-0033

    Article  PubMed  CAS  Google Scholar 

  17. Gupta MP (2007) Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure. J Mol Cell Cardiol 43:388–403. doi:10.1016/j.yjmcc.2007.07.045

    Article  PubMed  CAS  Google Scholar 

  18. Kim D, Smith TW (1984) Effects of thyroid hormone on sodium pump sites, sodium content, and contractile responses to cardiac glycosides in culture chick ventricular cells. J Clin Invest 74:1481–1488. doi:10.1172/JCI111561

    Article  PubMed  CAS  Google Scholar 

  19. Wolska BM, Averyhart-Fullard V, Omachi A, Stojanovic MO, Kallen RG, Solaro RJ (1997) Changes in thyroid state affect pHi and Na+i homeostasis in rat ventricular myocytes. J Mol Cell Cardiol 29:2653–2663. doi:10.1006/jmcc.1997.0495

    Article  PubMed  CAS  Google Scholar 

  20. Ismail-Beigi F, Edelman IS (1971) The mechanism of the calorigenic action of thyroid hormone. Stimulation of Na + -K + activated adenoinetriphosphatase activity. J Gen Physiol 57:710–722. doi:10.1085/jgp. 57.6.710

    Article  PubMed  CAS  Google Scholar 

  21. Brodie C, Sampson SR (1989) Characterization of thyroid hormone effects on Na channel synthesis in cultured skeletal myotubes: role of Ca2+. Endocrinology 125:842–849

    Article  PubMed  CAS  Google Scholar 

  22. Beekman RE, van Hardeveld C, Simonides WS (1988) Effect of thyroid statue on cytosolic free calcium in resting and electrically stimulated cardiac myocytes. Biochim Biophys Acta 969:18–27. doi:10.1016/0167-4889(88)90083-3

    Article  PubMed  CAS  Google Scholar 

  23. Lomax RB, Cobbold PH, Allshire AP, Cuthbertson KS, Robertson WR (1991) Tri-iodothyronine increases intra-cellular calcium levels in single rat myocytes. J Mol Endocrinol 7:77–79

    Article  PubMed  CAS  Google Scholar 

  24. Queiroz MS, Shao Y, Berkich DA, LaNoue KF, Ismail-Beigi F (2002) Thyroid hormone regulation of cardiac bioenergetics: role of intracellular creatine. Am J Physiol 283:H2527–H2533

    CAS  Google Scholar 

  25. Shao Y, Pressley TA, Ismail-Beigi F (1999) Na, K-ATPase mRNA β1 expression in rat myocardium-effect of thyroid status. Eur J Biochem 260:1–8. doi:10.1046/j.1432-1327.1999.00111.x

    Article  PubMed  CAS  Google Scholar 

  26. Cataldo NA, Cooper DS, Chin WW, Maloof F, Ridgway EC (1982) The effect of thyroid hormones on prolactin secretion by cultured bovine pituitary cells. Metabolism 31:589–594. doi:10.1016/0026-0495(82)90097-X

    Article  PubMed  CAS  Google Scholar 

  27. Akerman KE (1981) Inhibition and stimulation of respiration-linked Mg2+ efflux in rat heart mitochondria. J Bioenerg Biomembr 13:133–139. doi:10.1007/BF00763835

    Article  PubMed  CAS  Google Scholar 

  28. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurements with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  29. Fagan TE, Cefaratti C, Romani A (2004) Streptozotocin-induced diabetes impairs Mg2+ homeostasis and uptake in rat liver cells. Am J Physiol 286:E184–E193

    CAS  Google Scholar 

  30. Reed G, Cefaratti C, Berti-Mattera LN, Romani A (2008) Lack of insulin impairs Mg2+ homeostasis and transport in cardiac cells of streptozotocin-injected diabetic rats. J Cell Biochem 104:1034–1053

    Article  PubMed  CAS  Google Scholar 

  31. Romani A, Scarpa A (1992) Regulation of cell magnesium. Arch Biochem Biophys 298:1–12. doi:10.1016/0003-9861(92)90086-C

    Article  PubMed  CAS  Google Scholar 

  32. Koss KL, Putnam RW, Grubbs RD (1993) Mg2+ buffering in cultured chick ventricular myocytes: quantitation and modulation by Ca2+. Am J Physiol 264:C1259–C1269

    PubMed  CAS  Google Scholar 

  33. Terasaki M, Rubin H (1985) Evidence that intracellular magnesium is present in cells at a regulatory concentration for protein synthesis. Proc Natl Acad Sci USA 82:7324–7326. doi:10.1073/pnas.82.21.7324

    Article  PubMed  CAS  Google Scholar 

  34. Cech SY, Broaddus WC, Maguire ME (1980) Adenylate cyclase: the role of magnesium and other divalent cations. Mol Cell Biochem 33:67–92. doi:10.1007/BF00224572

    Article  PubMed  CAS  Google Scholar 

  35. Sousa VP, Pinto JR, Sorenson MM (2006) Ionic interventions that alter the association of troponin C C-domain with the thin filaments of vertebrate striated muscle. Biochim Biophys Acta 1760:272–282

    PubMed  CAS  Google Scholar 

  36. Duggleby RC, East M, Lee AG (1999) Luminal dissociation of Ca2+ from the phosphorylated Ca2+-ATPase is sequential and gated by Mg2+. Biochem J 339:351–357. doi:10.1042/0264-6021:3390351

    Article  PubMed  CAS  Google Scholar 

  37. Panov A, Scarpa A (1996) Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+. Biochemistry 35:427–432. doi:10.1021/bi952101t

    Article  PubMed  CAS  Google Scholar 

  38. Panov A, Scarpa A (1996) Mg2+ control of respiration in isolated rat liver mitochondria. Biochemistry 35:12849–12856. doi:10.1021/bi960139f

    Article  PubMed  CAS  Google Scholar 

  39. Nakashima RA, Dordick RS, Garlid KD (1982) On the relative roles of Ca2+ and Mg2+ in regulating the endogenous K+/H+ exchanger of rat liver mitochondria. J Biol Chem 257:12540–12545

    PubMed  CAS  Google Scholar 

  40. Goglia F, Silvestri E, Lami A (2001) Thyroid hormone and mitochondria. Biosci Rep 22:17–32. doi:10.1023/A:1016056905347

    Article  Google Scholar 

  41. Wiesenberger G, Waldhorr M, Schweyen RJ (1992) The nuclear gene MRS2 is essential for the excision of group II introns from yeast mitochondrial transcripts in vivo. J Biol Chem 267:6963–6969

    PubMed  CAS  Google Scholar 

  42. Kolisek M, Zsurka G, Samaj J, Weghuber J, Schweyen RJ, Schweigel M (2003) Mrs2p is an essential component of the major electrophoretic Mg2 + influx system in mitochondria. EMBO J 22:1235–1244. doi:10.1093/emboj/cdg122

    Article  PubMed  CAS  Google Scholar 

  43. Romani A (2007) Regulation of magnesium homeostasis and transport in mammalian cells. Arch Biochem Biophys 458:90–102. doi:10.1016/j.abb.2006.07.012

    Article  PubMed  CAS  Google Scholar 

  44. Jakob A, Becker J, Schottli G, Fritzsch G (1989) α1-Adrenergic stimulation causes Mg2+ release from perfused rat liver. FEBS Lett 246:127–130. doi:10.1016/0014-5793(89)80267-4

    Article  PubMed  CAS  Google Scholar 

  45. Levey GS, Epstein SE (1969) Myocardial adenyl cyclase: activation by thyroid hormones and evidence for two adenyl cyclase systems. J Clin Invest 48:1663–1669. doi:10.1172/JCI106131

    Article  PubMed  CAS  Google Scholar 

  46. Maguire ME (1984) Hormone-sensitive magnesium transport and magnesium regulation of adenylate cyclase. Trends Pharmacol Sci 5:73–77. doi:10.1016/0165-6147(84)90372-9

    Article  CAS  Google Scholar 

  47. Ririe DG, Butterworth JF, Royster RL, MAcGregor DA, Zaloga GP (1995) Triiodothyronine increases contractility independent of beta-adrenergic receptors or stimulation of cyclic-3’, 5’-adenosine monophosphate. Anesthesiology 82:1004–1012. doi:10.1097/00000542-199504000-00025

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by NIH-HL18708 and NIAAA-11593 to Dr. Andrea Romani.

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Authors and Affiliations

  1. School of Medicine-Department of Physiology and Biophysics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106-4970, USA

    Brandon Ballard, Lisa M. Torres & Andrea Romani

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  1. Brandon Ballard
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  2. Lisa M. Torres
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  3. Andrea Romani
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Correspondence to Andrea Romani.

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Ballard, B., Torres, L.M. & Romani, A. Effect of thyroid hormone on Mg2+ homeostasis and extrusion in cardiac cells. Mol Cell Biochem 318, 117–127 (2008). https://doi.org/10.1007/s11010-008-9863-9

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