TY - JOUR
TI - Thyroxine pretreatment increases basal myocardial heat-shock protein 27 expression and accelerates translocation and phosphorylation of this protein upon ischaemia
AU - Pantos, C.
AU - Malliopoulou, V.
AU - Mourouzis, I.
AU - Karamanoli, E.
AU - Moraitis, P.
AU - Tzeis, S.
AU - Paizis, I.
AU - Cokkinos, A.D.
AU - Carageorgiou, H.
AU - Varonos, D.D.
AU - Cokkinos, D.V.
JO - European Journal of Pharmacology
PY - 2003
VL - 478
TODO - 1
SP - 53-60
PB - 
SN - 0014-2999
TODO - 10.1016/j.ejphar.2003.08.030
TODO - 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
TODO - 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.
ER -