Bačová Barbara Szeiffová, Vinczenzová Csilla, Žurmanová Jitka, Kašparová Dita, Knezl Vladimír, Beňová Tamara Egan, Pavelka Stanislav, Soukup Tomáš, Tribulová Narcisa
Institute for Heart Research, Slovak Academy of Sciences, Dúbravská cesta 9, POBox 104, 840 05, Bratislava, Slovak Republic.
Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.
Histochem Cell Biol. 2017 Jan;147(1):63-73. doi: 10.1007/s00418-016-1488-6. Epub 2016 Sep 6.
We aimed to study the impact of altered thyroid status on myocardial expression of electrical coupling protein connexin-43 (Cx43), the susceptibility of rats to ventricular fibrillation (VF) and the effects of antioxidant-rich red palm oil (RPO). Adult male and female euthyroid, hyperthyroid (treated with T/T), hypothyroid (treated with methimazole) Wistar rats supplemented or not with RPO for 6 weeks were used. Function of isolated perfused heart and VF threshold were determined. Left ventricular tissue was used for assessment of mRNA and protein levels of Cx43, its phosphorylated forms and topology. Protein kinase C signaling (PKC) and gene transcripts of some proteins related to cardiac arrhythmias were assessed. Hyperthyroid state resulted in decrease of total and phosphorylated forms of Cx43 and suppression of PKC-ε expression in males and females, decrease of Cx43 mRNA in females, decrease of VF threshold and increase of functional parameters in male rat hearts. In contrast, hypothyroid status resulted in the increase of total and phosphorylated forms of Cx43, enhancement PKC-ε expression in males and females, increase of Cx43 mRNA in females, increase of VF threshold and decrease of functional parameters in male rat hearts. Function of the heart was partially normalized by RPO intake, which also enhanced myocardial Cx43 and PKC-ε expression as well as increased VF threshold in hyperthyroid male rats. We conclude that there is an inverse relationship between myocardial expression of Cx43, including its functional phosphorylated forms, and susceptibility of male rat hearts to VF in condition of altered thyroid status. RPO intake partly ameliorated adverse changes caused by excess of thyroid hormones.
我们旨在研究甲状腺状态改变对电偶联蛋白连接蛋白43（Cx43）心肌表达的影响、大鼠对室颤（VF）的易感性以及富含抗氧化剂的红棕榈油（RPO）的作用。使用成年雄性和雌性甲状腺功能正常、甲状腺功能亢进（用T/T治疗）、甲状腺功能减退（用甲巯咪唑治疗）的Wistar大鼠，补充或不补充RPO，持续6周。测定离体灌注心脏的功能和室颤阈值。左心室组织用于评估Cx43及其磷酸化形式和拓扑结构的mRNA和蛋白质水平。评估蛋白激酶C信号传导（PKC）和一些与心律失常相关蛋白质的基因转录本。甲状腺功能亢进状态导致雄性和雌性Cx43的总形式和磷酸化形式减少，PKC-ε表达受抑制，雌性Cx43 mRNA减少，雄性大鼠心脏室颤阈值降低，功能参数增加。相反，甲状腺功能减退状态导致Cx43的总形式和磷酸化形式增加，雄性和雌性PKC-ε表达增强，雌性Cx43 mRNA增加，雄性大鼠心脏室颤阈值增加，功能参数降低。摄入RPO可使心脏功能部分恢复正常，这也增强了甲状腺功能亢进雄性大鼠的心肌Cx43和PKC-ε表达，并提高了室颤阈值。我们得出结论，在甲状腺状态改变的情况下，包括其功能性磷酸化形式在内的Cx43心肌表达与雄性大鼠心脏对室颤的易感性之间存在负相关关系。摄入RPO部分改善了甲状腺激素过量引起的不良变化。
