Thyroxine pretreatment increases basal myocardial heat-shock protein 27 expression and accelerates translocation and phosphorylation of this protein upon ischaemia.
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 (T(4)) was administered to Wistar rats (25 microg/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.
Pantos
Constantinos
C
Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527 Goudi, Athens, Greece. cpantos@cc.uoa.gr
Malliopoulou
Vassiliki
V
Mourouzis
Iordanis
I
Karamanoli
Evangelia
E
Moraitis
Panagiotis
P
Tzeis
Stylianos
S
Paizis
Ioannis
I
Cokkinos
Alexandros D
AD
Carageorgiou
Hariclia
H
Varonos
Dennis D
DD
Cokkinos
Dennis V
DV
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000008:administration & dosage*
D006360:Heat-Shock Proteins; D013974:Thyroxine