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Thyroid hormone and cardioprotection: Study of p38 MAPK and JNKs during ischaemia and at reperfusion in isolated rat heart

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Abstract

It has been recently shown that long-term thyroxine administration increases the tolerance of the heart to ischaemia. The present study investigated whether thyroxine induced cardioprotection involves alterations in the pattern of p38 mitogen activated protein kinase (p38MAPK) and c-Jun NH2-terminal kinases (JNKs) activation during ischaemia-reperfusion. L-thyroxine (T4) was administered in Wistar rats (25 μg/100 g/day, subcutaneously) for 2 weeks (THYR), while normal animals served as controls (NORM). NORM and THYR isolated rat hearts were perfused in Langendorff mode and subjected to 10 or 20 min of zero-flow global ischaemia only and also to 20 min of ischaemia followed by 10, 20 or 45 min of reperfusion. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value. Activation of p38 MAPK and JNKs was assessed at the different times of the experimental setting by standard Western blotting techniques using a dual phospho p38MAPK and phospho JNKs (p46/p54) antibodies. Activation of p38 MAPK was significantly attenuated during ischaemia and reperfusion in thyroxine treated hearts compared to normal hearts. JNKs were found to be activated only during the reperfusion period. The levels of phospho JNKs were found to be lower in thyroxine treated hearts as compared to untreated hearts, though not at a statistically significant level. Postischaemic functional recovery was higher in THYR as compared to NORM, p < 0.05. In summary, in hearts pretreated with thyroxine, p38 MAPK was attenuated during ischaemia and at reperfusion and this was associated with improved postischaemic recovery of function.

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References

  1. Nakano A, Cohen MV, Downey JM: Ischemic preconditioning: From basic mechanisms to clinical applications. Pharmacol Ther 86: 263-275, 2000

    Google Scholar 

  2. Pantos C, Malliopoulou V, Mourouzis I, Karamanoli E, Tzeis SM, Carageorgiou H, Varonos D, Cokkinos DV: Long-term thyroxine administration increases HSP70 mRNA expression and attenuates p38 MAP kinase activity in response to ischaemia. J Endocrinol 170: 207-215, 2001

    Google Scholar 

  3. Pantos C, Cokkinos DD, Tzeis S, Malliopoulou V, Mourouzis I, Carageorgiou H, Limas C, Varonos D, Cokkinos D: Hyperthyroidism is associated with preserved preconditioning capacity but intensified and accelerated ischaemic contracture in rat heart. Basic Res Cardiol 94: 254-260, 1999

    Google Scholar 

  4. Klein I, Ojamaa K: Thyroid hormone — targeting the heart. Endocrinology 142: 11-12, 2001

    Google Scholar 

  5. Fryer LGD, Holness MJ, Decock JB, Sugden MC: Cardiac protein kinase C expression in two models of cardiac hypertrophy associated with an activated cardiac renin-angiotensin system: Effect of experimental hyperthyroidism and genetic hypertension (the mRen-2 rat). J Endocrinol 158: 27-33, 1998

    Google Scholar 

  6. Pantos C, Malliopoulou V, Mourouzis I, Karamanoli E, Paizis I, Steimberg N, Varonos D, Cokkinos DV: Long-term thyroxine administration protects the heart in a similar pattern as ischaemic preconditioning. Thyroid 12: 325-329, 2002

    Google Scholar 

  7. Han J, Lee J-D, Bibbs L, Ulevitch RJ: A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265: 808-811, 1994

    Google Scholar 

  8. Bogoyevitch M, Gillespie-Brown J, Ketterman A, Fuller S, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH: Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart: p38/RK mitogen-activated protein kinases and c-jun N-Terminal kinases are activated by ischemia/reperfusion. Circ Res 79: 162-173, 1996

    Google Scholar 

  9. Yin T, Sandhu G, Wolfgang C, Burrier A, Randy LW, Rigel DF, Tsonwin H, Whelan J: Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney. J Biol Chem 272: 19943-19950, 1997

    Google Scholar 

  10. Knight RJ, Buxton DB: Stimulation of c-Jun kinase and mitogen-activated protein kinase by ischaemia and reperfusion in the perfused rat heart. Biochem Biophys Res Commun 218: 83-88, 1996

    Google Scholar 

  11. Chen Y-R, Wang X, Templeton D, Davis RJ, Tan T-H: The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and γ radiation. J Biol Chem 271: 31929-31936, 1996

    Google Scholar 

  12. Mackay K, Mochly-Rosen D: An inhibitor of p38 mitogen-activated protein kinase protects neonatal cardiac myocytes from ischemia. J Biol Chem 274: 6272-6279, 1999

    Google Scholar 

  13. Nagarkatti D, Sha'afi R: Role of p38 MAP kinase in myocardial stress. J Mol Cell Cardiol 30: 1651-1664, 1998

    Google Scholar 

  14. Marais E, Genade S, Huisamen B, Strijdom JG, Moolman JA, Lochner A: Activation of p38 MAPK induced by a multicycle ischaemic preconditioning protocol is associated with attenuated p38 MAPK activity during sustained ischaemia and reperfusion. J Mol Cell Cardiol 33: 769-778, 2001

    Google Scholar 

  15. Ma XL, Kumar S, Gao F et al.: Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 99: 1685-1691, 1999

    Google Scholar 

  16. Pantos CI, Tzilalis V, Giannakakis S, Cokkinos DD, Tzeis SM, Malliopoulou V, Mourouzis I, Asimacopoulos P, Carageorgiou H, Varonos DD, Cokkinos DV: Phenylephrine induced aortic vasoconstriction is attenuated in hyperthyroid rats. Int Angiol 20: 181-186, 2001

    Google Scholar 

  17. Pantos C, Mourouzis I, Tzeis S, Malliopoulou V, Cokkinos DD, Asimakopoulos P, Carageorgiou H, Varonos DD, Cokkinos DV: Propranolol diminishes cardiac hypertrophy but does not abolish acceleration of the ischemic contracture in hyperthyroid hearts. J Cardiovasc Pharmacol 36: 384-389, 2000

    Google Scholar 

  18. Schneider S, Chen W, Hou J, Steenbergen C, Murphy E: Inhibition of p38 MAPK α/β reduces ischemic injury and does not block protective effects of preconditioning. Am J Physiol Heart Circ Physiol 280: H499-H508, 2001

    Google Scholar 

  19. Marais E, Genade S, Strijdom JG, Moolman JA, Lochner A: p38 MAPK activation triggers pharmacologically-induced beta-adrenergic preconditioning, but not ischaemic preconditioning. J Mol Cell Cardiol 33: 2157-2177, 2001

    Google Scholar 

  20. Saurin AT, Martin JL, Heads RJ, Foley C, Mockridge W, Wright MJ, Wang Y, Marber MS: The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes FASEB J 14: 2237-2246, 2000

    Google Scholar 

  21. Van Der Vusse GJ, Coumans WA, Ulrich M, Van Bilsen M: Thyroxine induced alteration in cardiac energy metabolism. J Moll Cell Cardiol 30: A110, 1998

    Google Scholar 

  22. Kolocassides KG, Galinanes M, Hearse DJ: Dichotomy of ischaemic preconditioning. Improved postischaemic contractile function despite intensification of ischaemic contracture. Circulation 93: 1725-1733, 1996

    Google Scholar 

  23. Asimakis GK, Conti VR: Preconditioning with dobutamine in the isolated rat heart. Life Sci 57: 177-187, 1995

    Google Scholar 

  24. Hearse DJ, Sutherland FJ: Catecholamines and preconditioning: Studies on contraction and function in isolated rat hearts. Am J Physiol 277: H136-H143, 1999

    Google Scholar 

  25. Gabai VL, Meriin AB, Yaglom JA, Wei JY, Mosser DD, Sherman MY: Suppression of stress kinase JNK is involved in HSP72-mediated protection of myogenic cells from transient energy deprivation: HSP72 alleviates the stress-induced inhibition of JNK dephosphorylation. J Biol Chem 275: 38088-38094, 2000

    Google Scholar 

  26. Sato M, Cordis G, Maulik N, Das DK: SAPKs regulation of ischemic preconditioning. Am J Physiol Heart Circ Physiol 279: H901-H907, 2000

    Google Scholar 

  27. Mackay K, Mochly-Rosen D: Involvement of a p38 mitogen-activated protein kinase phosphatase in protecting neonatal rat cardiac myocytes from ischemia. J Moll Cell Cardiol 32: 1585-1588, 2000

    Google Scholar 

  28. Kimura T, Kanda T, Kotajima N, Kuwabara A, Fukumura Y, Kobayashi I: Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction. Eur J Endocrinol 143: 179-184, 2000

    Google Scholar 

  29. Friberg L, Drvota V, Bjelak AH, Eggertsen G, Ahnvc S: Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction. Am J Med 111: 699-703, 2001

    Google Scholar 

  30. 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 279: E1319-E1324, 2000

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527, Goudi, Athens, Greece

    Constantinos Pantos, Vassiliki Malliopoulou, Ioannis Paizis, Panagiotis Moraitis, Iordanis Mourouzis, Stylianos Tzeis, Evangelia Karamanoli, Demosthenes D. Cokkinos, Hariclia Carageorgiou & Dennis Varonos

  2. 1st Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Avenue, 17674, Kallithea, Athens, Greece

    Dennis V. Cokkinos

Authors
  1. Constantinos Pantos
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  2. Vassiliki Malliopoulou
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  3. Ioannis Paizis
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  4. Panagiotis Moraitis
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  5. Iordanis Mourouzis
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  6. Stylianos Tzeis
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  7. Evangelia Karamanoli
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  8. Demosthenes D. Cokkinos
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  9. Hariclia Carageorgiou
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  10. Dennis Varonos
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  11. Dennis V. Cokkinos
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Pantos, C., Malliopoulou, V., Paizis, I. et al. Thyroid hormone and cardioprotection: Study of p38 MAPK and JNKs during ischaemia and at reperfusion in isolated rat heart. Mol Cell Biochem 242, 173–180 (2003). https://doi.org/10.1023/A:1021162417490

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