Τίτλος:
Thyroxine pretreatment increases basal myocardial heat-shock protein 27 expression and accelerates translocation and phosphorylation of this protein upon ischaemia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Pantos, C.
Malliopoulou, V.
Mourouzis, I.
Karamanoli, E.
Moraitis, P.
Tzeis, S.
Paizis, I.
Cokkinos, A.D.
Carageorgiou, H.
Varonos, D.D.
Cokkinos, D.V.
Περιοδικό:
European Journal of Pharmacology
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.ejphar.2003.08.030
