@article{3022742, title = "Thyroxine pretreatment increases basal myocardial heat-shock protein 27 expression and accelerates translocation and phosphorylation of this protein upon ischaemia", author = "Pantos, C. and Malliopoulou, V. and Mourouzis, I. and Karamanoli, E. and Moraitis, P. and Tzeis, S. and Paizis, I. and Cokkinos, A.D. and Carageorgiou, H. and Varonos, D.D. and Cokkinos, D.V.", journal = "European Journal of Pharmacology", year = "2003", volume = "478", number = "1", pages = "53-60", issn = "0014-2999", doi = "10.1016/j.ejphar.2003.08.030", keywords = "heat shock protein 27; levothyroxine, animal experiment; animal model; animal tissue; article; blood flow; controlled study; cytoskeleton; cytosol; heart left ventricle; heart muscle ischemia; heart muscle reperfusion; isolated heart; male; nonhuman; pressure; priority journal; protein expression; protein phosphorylation; rat; statistical significance, Animals; Gene Expression Regulation; Heat-Shock Proteins; Male; Myocardial Ischemia; Myocardium; Phosphorylation; Protein Transport; Rats; Rats, Wistar; Thyroxine", abstract = "Thyroxine pretreatment increases the tolerance of the heart to ischaemia, and heat-shock protein 27 (HSP27) is considered to play an important role in cardioprotection. The present study investigated whether long-term thyroxine administration can induce changes in the expression, translocation and phosphorylation of HSP27 at baseline and upon ischaemic stress. L-Thyroxine (T4) was administered to Wistar rats (25 μg/100 g/day s.c.) for 2 weeks, while normal animals served as controls. Hearts from normal and thyroxine-treated rats were perfused in Langendorff mode and subjected to 10 or 20 min of zero-flow global ischaemia only or to 20 min of ischaemia followed by 45 min of reperfusion. Total and phospho-HSP27 expression were assessed at different times in the Triton-soluble (cytosol-membrane), S fraction, and the Triton-insoluble (cytoskeleton-nucleus) fraction, P fraction. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value. In hearts from thyroxine-treated animals, the levels of basal total HSP27 and phospho-HSP27 in the P fraction were significantly increased as compared to normal. In response to ischaemia, in hearts from thyroxine-treated rats, the levels of total HSP27 and phospho-HSP27 were found to be significantly increased in the P fraction at 10 and 20 min of ischaemia as compared to preischaemic values, whereas in normal hearts, the levels of total HSP27 and phospho-HSP27 were significantly increased at 20 min only. Postischaemic functional recovery was significantly greater in thyroxine-treated than in untreated hearts. In summary, long-term thyroxine pretreatment results in an increased basal expression and phosphorylation of HSP27 and in an earlier and sustained redistribution of HSP27 from the S to the P fraction in response to ischaemia. This effect might be of important therapeutic relevance. © 2003 Elsevier B.V. All rights reserved." }