Thyroid hormone and cardioprotection: study of p38 MAPK and JNKs during ischaemia and at reperfusion in isolated rat heart.
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 microg/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.
Pantos
Constantinos
C
Department of Pharmacology, University of Athens, Goudi, Athens, Greece. cpantos@cc.uoa.gr
Malliopoulou
Vassiliki
V
Paizis
Ioannis
I
Moraitis
Panagiotis
P
Mourouzis
Iordanis
I
Tzeis
Stylianos
S
Karamanoli
Evangelia
E
Cokkinos
Demosthenes D
DD
Carageorgiou
Hariclia
H
Varonos
Dennis
D
Cokkinos
Dennis V
DV
D000818:Animals; D004789:Enzyme Activation; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D013963:Thyroid Hormones; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013974:Thyroxine