The present study was undertaken to investigate heat stress protein (HSP)-70 mRNA induction and p38 MAP kinase (MAPK) activity in response to ischaemic stress in the hyperthyroid rat heart. L-Thyroxine (T(4)) (25 microg/100 g body weight) was administered to Wistar rats for 2 days (THYRacute) or 14 days (THYR), while animals treated similarly with normal saline served as controls (NORMacute and NORM). In addition, abdominal aortic banding was performed in another group of rats to produce constriction-induced hypertrophy (HYP), while sham-operated (SOP) animals served as controls. Isolated rat hearts were perfused in a Langendorff mode. Hearts from NORMacute (n=6), THYRacute animals (n=8), NORM (n=6), THYR (n=6), SOP (n=5) and HYP (n=7) animals were subjected to 20 min of zero-flow global ischaemia followed by 45 min of reperfusion. HSP70 mRNA expression and phosphorylated p38 MAPK protein expression were detected in response to ischaemia and protein kinase C-epsilon (PKCepsilon) protein expression was detected at baseline. Thyroid hormones were measured in plasma. Long-term T(4) administration and aortic constriction resulted in the development of cardiac hypertrophy. Thyroid hormones were increased in both THYR and THYRacute as compared with normal groups (P<0.05). HSP70 mRNA induction was increased 2.3-fold in THYR as compared with NORM hearts (P<0.05), whereas there was not any difference between THYRacute and NORMacute hearts (P>0.05). Phosphorylated p38 MAPK protein expression was 2.2-fold more in NORM than in THYR hearts (P<0.05), but it was not different between NORMacute and THYRacute hearts (P>0.05). HSP70 mRNA induction was 1.8-fold greater in HYP than in SOP hearts (P<0.05), whereas phosphorylated p38 MAPK protein expression was similar between the two groups (P>0.05). PKCepsilon protein expression at baseline was 1.7-fold more in NORM than in THYR hearts (P<0.05), and not different between NORMacute and THYRacute hearts (P>0.05) as well as HYP and SOP hearts (P>0.05). This study shows that HSP70 mRNA expression is increased, whereas p38 MAPK activation is attenuated in response to ischaemia in long-term T(4)-treated rat hearts as compared with normal and acute hyperthyroid hearts.
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CI Pantos, VA Malliopoulou, IS Mourouzis, EP Karamanoli, SM Tzeis, HC Carageorgiou, DD Varonos, and DV Cokkinos
C Pantos, V Malliopoulou, I Mourouzis, K Sfakianoudis, S Tzeis, P Doumba, C Xinaris, AD Cokkinos, H Carageorgiou, DD Varonos, and DV Cokkinos
The present study investigated the response of the hypothyroid heart to ischaemia-reperfusion. Hypothyroidism was induced in Wistar rats by oral administration of propylthiouracil (0.05%) for 3 weeks (HYPO rats), while normal animals (NORM) served as controls. Isolated hearts from NORM and HYPO animals were perfused in Langendorff mode and subjected to zero-flow global ischaemia followed by reperfusion (I/R). Post-ischaemic recovery of left ventricular developed pressure was expressed as % of the initial value (LVDP%). Basal expression of protein kinase C epsilon (PKCepsilon) and PKCdelta and phosphorylation of p46 and p54 c-jun NH(2)-terminal kinases (JNKs) in response to I/R were assessed by Western blotting. LVDP% was found to be significantly higher in HYPO hearts than in NORM. At baseline, PKCepsilon expression was 1.4-fold more in HYPO than in NORM hearts, P<0.05, while PKCdelta was not changed. Furthermore, basal phospho-p54 and -p46 JNK levels were 2.2- and 2.6-fold more in HYPO than in NORM hearts, P<0.05. In response to I/R, in NORM hearts, phospho-p54 and -p46 JNK levels were 5.5- and 6.0-fold more as compared with the baseline values, P<0.05, while they were not significantly altered in HYPO hearts. HYPO hearts seem to display a phenotype of cardioprotection against ischaemia-reperfusion and this is associated with basal PKCepsilon overexpression and attenuated JNK activation after I/R.