PMID- 12967335 OWN - NLM STAT- MEDLINE DCOM- 20031204 LR - 20190709 IS - 0022-0795 (Print) IS - 0022-0795 (Linking) VI - 178 IP - 3 DP - 2003 Sep TI - Propylthiouracil-induced hypothyroidism is associated with increased tolerance of the isolated rat heart to ischaemia-reperfusion. PG - 427-35 AB - 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. FAU - Pantos, C AU - Pantos C AD - Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527 Goudi, Athens, Greece. cpantos@cc.uoa.gr FAU - Malliopoulou, V AU - Malliopoulou V FAU - Mourouzis, I AU - Mourouzis I FAU - Sfakianoudis, K AU - Sfakianoudis K FAU - Tzeis, S AU - Tzeis S FAU - Doumba, P AU - Doumba P FAU - Xinaris, C AU - Xinaris C FAU - Cokkinos, A D AU - Cokkinos AD FAU - Carageorgiou, H AU - Carageorgiou H FAU - Varonos, D D AU - Varonos DD FAU - Cokkinos, D V AU - Cokkinos DV LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 721M9407IY (Propylthiouracil) RN - EC 2.7.1.- (Prkce protein, rat) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (Protein Kinase C-epsilon) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Animals MH - Blotting, Western/methods MH - Hypothyroidism/*complications/metabolism MH - *JNK Mitogen-Activated Protein Kinases MH - MAP Kinase Kinase 4 MH - Male MH - Mitogen-Activated Protein Kinase Kinases/analysis/metabolism MH - Models, Animal MH - Myocardial Contraction MH - Myocardial Reperfusion Injury/*complications/metabolism MH - Myocardium/metabolism MH - Perfusion MH - Phosphorylation MH - Propylthiouracil MH - Protein Kinase C/metabolism MH - Protein Kinase C-epsilon MH - Rats MH - Rats, Wistar MH - Ventricular Pressure EDAT- 2003/09/12 05:00 MHDA- 2003/12/05 05:00 CRDT- 2003/09/12 05:00 PHST- 2003/09/12 05:00 [pubmed] PHST- 2003/12/05 05:00 [medline] PHST- 2003/09/12 05:00 [entrez] AID - 10.1677/joe.0.1780427 [doi] PST - ppublish SO - J Endocrinol. 2003 Sep;178(3):427-35. doi: 10.1677/joe.0.1780427.