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Horm Metab Res 2006; 38(5): 308-313
DOI: 10.1055/s-2006-925404
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Hyperthyroid Hearts Display a Phenotype of Cardioprotection Against Ischemic Stress: A Possible Involvement of Heat Shock Protein 70

C.  Pantos1 , V.  Malliopoulou1 , I.  Mourouzis1 , A.  Thempeyioti1 , I.  Paizis1 , A.  Dimopoulos1 , T.  Saranteas1 , C.  Xinaris1 , D.  V.  Cokkinos2
  • 1Department of Pharmacology, University of Athens
  • 21st Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece
Further Information

Publication History

Received 4 October 2005

Accepted after revision 21 December 2005

Publication Date:
23 May 2006 (online)

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Abstract

Hyperthyroid hearts are shown to display a phenotype of cardioprotection against ischemic stress, but the underlying signaling mechanisms remain largely unknown. The present study investigated the possible relation of HSP70 to the thyroid hormone induced cardioprotection. HSP70 is a redox-regulated molecular chaperone, and enhances cell survival under stress. Thyroxin (25 µg/100 g body weight) was administered to Wistar male rats for four days (THYR-4d) and two weeks (THYR-14d), respectively, while untreated animals served as controls (CON-4d, CON-14d). Isolated hearts from control and thyroxin treated rats were subjected to 20 min zero-flow ischemia followed by 45 min of reperfusion (I/R). The amount of HSP70 in the myocardium for THYR-14d was 1.85 times the levels of CON-14d (p < 0.05). The levels of HSP70 expression were no different between THYR-4d and CON-4d, p > 0.05. This was only accompanied by an increase in MDA levels (used as an index of oxidative stress) in THYR-14d compared to untreated hearts. These changes corresponded to a differential response of the heart to I/R; post-ischemic recovery of function was significantly increased in THYR-14d compared to CON-14d, and was no different between the THYR-4d and CON-4d hearts. In conclusion, long-term thyroxin administration results in increased tolerance of the myocardium to I/R and enhances the expression of HSP70 which may, at least in part, account for this response.

Key words

Thyroid hormone - heat shock proteins - heat stress - oxidative stress - ischemia reperfusion

References

  • 1 Kahaly G J, Dillman W H. Thyroid hormone action in the heart.  Endocrine reviews. 2005;  26 704-728
    CrossrefPubMedGoogle Scholar
  • 2 Pantos C, Malliopoulou V, Varonos D, Cokkinos D V. Thyroid hormone and phenotypes of cardioprotection.  Basic Res Cardiol. 2004;  99 101-120
    CrossrefPubMedGoogle Scholar
  • 3 Buser P T, Wikman-Coffelt J, Wu S T, Derugin N, Parmley W W, Higgins C B. Postischemic recovery of mechanical performance and energy metabolism in the presence of left ventricular hypertrophy. A 31P-NMR study.  Circ Res. 1990;  66(3) 735-746
    PubMedGoogle Scholar
  • 4 Pantos C, Malliopoulou V, Mourouzis I, Karamanoli E, Paizis I, Steimberg N, Varonos D, Cokkinos D V. Long-term Thyroxine Administration Protects the Heart in a Similar Pattern as Ischemic Preconditioning.  Thyroid. 2002;  12 325-329. Rapid communication
    CrossrefPubMedGoogle Scholar
  • 5 Pantos C, Malliopoulou V, Paizis I, Moraitis P, Mourouzis I, Tzeis S, Karamanoli E, Cokkinos D D, Carageorgiou H, Varonos D, Cokkinos D V. Thyroid hormone and cardioprotection; study of p38 MAPK and JNKs during ischemia and at reperfusion in isolated rat heart.  Molecular and Cellular Biochemistry. 2003;  242 173-180
    CrossrefPubMedGoogle Scholar
  • 6 Pantos C, Malliopoulou V, Mourouzis I, Karamanoli E, Moraitis P, Tzeis S, Paizis I, Carageorgiou H, Varonos D, Cokkinos D V. Thyroxine pretreatment increases basal myocardial HSP27 expression and accelerates translocation and phosphorylation of this protein upon ischemia.  Eur J Pharmacol. 2003;  478 53-60
    CrossrefPubMedGoogle Scholar
  • 7 Kuzman J A, Gerdes A M, Kobayashi S, Liang Q. Thyroid hormone activates Akt and prevents serum starvation-induced cell death in neonatal rat cardiomyocytes.  J Mol Cell Cardiol. 2005;  39(5) 841-844
    CrossrefPubMedGoogle Scholar
  • 8 Zinman T, Shneyvays V, Tribulova N, Manoach M, Shainberg A. Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes.  J Cell Physiol. 2005;  (in press)
    PubMedGoogle Scholar
  • 9 Ojamaa K, Kenessey A, Shenoy R, Klein I. Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat.  Am J Physiol. 2000;  279(6) E1319-1324
    PubMedGoogle Scholar
  • 10 Dimitriadis G, Maratou E, Alevizaki M, Boutati E, Psara K, Papasteriades C, Raptis S A. Thyroid hormone excess increases basal and insulin-stimulated recruitment of GLUT3 glucose transporters on cell surface.  Horm Metab Res.. 2005;  37(1) 15-20
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Gray C C, Amrani M, Yacoub M H. Heat stress proteins and myocardial protection: experimental model or potential clinical tool?.  The International J Biochem Cell Biol. 1999;  31 559-573
    PubMedGoogle Scholar
  • 12 Papp E, Nardai G, Soti C, Csermely P. Molecular chaperones, stress proteins and redox homeostasis.  Biofactors. 2003;  17 249-257
    PubMedGoogle Scholar
  • 13 Kukreja R C, Kontos M C, Loesser K E, Batra S K, Qian Y Z, Gbur C J jr, Naseem S A, Jesse R L, Hess M L. Oxidant stress increases heat shock protein 70 mRNA in isolated perfused rat heart.  Am J Physiol. 1994;  267(6 Pt 2) H2213-2219
    PubMedGoogle Scholar
  • 14 Marber M S, Walker J M, Latchman D S, Yellon D M. Myocardial protection following whole body heat stress in the rabbit is dependent on metabolic substrate and is related to the amount of the inducible 70 kb Dalton heat shock protein.  J Clin Invest. 1994;  93 1087-1094
    PubMedGoogle Scholar
  • 15 Mestril R, Chi S H, Sayen R, O R eilly, Dillmann W H. Expression of inducible stress protein 70 in heart myogenic cells confers protection against simulated iscahemia-induced injury.  J Clin Invest. 1994;  93 759-767
    PubMedGoogle Scholar
  • 16 Chen Y, Arrigo A-P, Currie R W. Heat shock treatment suppresses angiotensin II-induced activation of NF-kB pathway and heart inflammation: a role for Ikk depletion by heat shock?.  Am J Physiol. 2004;  287 H1104-H1114
    PubMedGoogle Scholar
  • 17 Pantos C, Mourouzis I, Saranteas T, Paizis I, Xinaris C, Malliopoulou V, Cokkinos D V. Thyroid hormone receptors alpha1 and beta1 are downregulated in the post-infarcted rat heart: consequences on the response to ischemia-reperfusion.  Basic Res Cardiol.. 2005;  100(5) 422-432
    CrossrefPubMedGoogle Scholar
  • 18 Morkin E, Ladenson P, Goldman S, Adamson C. Thyroid hormone analogs for treatment of hypercholesterolemia and heart failure: past, present and future prospects.  J Mol Cell Cardiol. 2004;  37 1137-1146
    PubMedGoogle Scholar
  • 19 Pantos C, Paizis I, Mourouzis I, Moraitis P, Tzeis S, Karamanoli E, Mourouzis C, Karageorgiou H, Cokkinos D V. Blockade of angiotensin II type 1 receptor diminishes cardiac hypertrophy, but does not abolish thyroxin-induced preconditioning.  Horm Metab Res. 2005;  37(8) 500-504
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Arrigo A P. In search of the molecular mechanism by which small stress proteins counteract apoptosis during cellular differentiation.  J Cell Biochem. 2005;  94(2) 241-246. Review
    CrossrefPubMedGoogle Scholar
  • 21 Manalo D J, Lin Z, Liu A Y. Redox-dependent regulation of the conformation and function of human heat shock factor 1.  Biochemistry. 2002;  41(8) 2580-2588
    CrossrefPubMedGoogle Scholar
  • 22 Barrett M J, Alones V, Wang K X, Phan L, Swerdlow R H. Mitochondria-derived oxidative stress induces a heat shock protein response.  J Neurosci Res. 2004;  78(3) 420-429
    CrossrefPubMedGoogle Scholar
  • 23 McDuffee A T, Senisterra G, Huntley S, Lepock J R, Sekhar K R, Meredith M J, Borrelli M J, Morrow J D, Freeman M L. Proteins containing disulfide bonds generated by oxidative stress can act as signals for the induction of the heat shock response.  J Cell Physiol. 1997;  171 143-151
    CrossrefPubMedGoogle Scholar
  • 24 Jacquier-Sarlin M R, Polla B S. Dual regulation of heat-shock transcription factor (HSF) activation and DNA-binding activity by H2O2: role of thioredoxin.  Biochem J. 1996;  318 ( Pt 1) 187-193
    PubMedGoogle Scholar
  • 25 Venditti P, De Rosa R, Di Meo S. Effect of thyroid state on susceptibility to oxidants and swelling of mitochondria from rat tissues.  Free Radic Biol Med. 2003;  35(5) 485-494
    CrossrefPubMedGoogle Scholar
  • 26 Yehuda-Shnaidman E, Kalderon B, Bar-Tana J. Modulation of mitochondrial transition pore components by thyroid hormone.  Endocrinology. 2005;  146(5) 2462-2472
    CrossrefPubMedGoogle Scholar
  • 27 Duntas L H. Oxidants, antioxidants in physical exercise and relation to thyroid function.  Horm Metab Res.. 2005;  37(9) 572-576. Review
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Pantos C, Malliopoulou V, Mourouzis I, Moraitis P, Tzeis S, Thempeyioti A, Paizis I, Cokkinos A D, Carageorgiou H, Varonos D, Cokkinos D V. Involvement of p38 MAPK and JNK in the heat stress induced cardioprotection.  Basic Res Cardiol. 2003;  98 158-164
    PubMedGoogle Scholar
  • 29 Latchman D S. Heat shock proteins and cardiac protection.  Cardiovasc Res. 2001;  51 637-646
    CrossrefPubMedGoogle Scholar
  • 30 Gabai V L, Yaglom J A. Hsp 72 mediated suppression of c -Jun N terminal kinase is implicated in the development of tolerance to caspace-independent cell death.  Mol Cell Biol. 2000;  20 6826-6836
    CrossrefPubMedGoogle Scholar
  • 31 Gabai V L, Meriin A B, Yaglom J A, Wei J Y, Mosser D D, Sherman M Y. Suppression of stress kinase JNK is involved in hsp72-mediated protection of myogenic cells from transient energy deprivation: HSP70 alleviates the stress induced inhibition of JNK dephosphorylation.  J Biol Chem. 2000;  275(48) 38 088-38 094
    PubMedGoogle Scholar
  • 32 Baxter J D, Webb P, Grover G, Scanlan T S. Selective action of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight.  Trends Endocrinol Metab. 2004;  15(4) 154-157
    CrossrefPubMedGoogle Scholar
  • 33 Pantos C, Mourouzis I, Malliopoulou V, Paizis I, Tzeis S, Moraitis P, Sfakianoudis K, Varonos D D, Cokkinos D V. Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor alpha1.  Thyroid. 2005;  15(1) 16-23
    CrossrefPubMedGoogle Scholar

Constantinos Pantos

Department of Pharmacology

University of Athens · 75 Mikras Asias Ave. · 11527 Goudi · Athens · Greece

Fax: +30 (21) 07 70 51 85

Email: cpantos@cc.uoa.gr