Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil.
Mol Cell Endocrinol. 2013 Aug 25;376(1-2):43-50. doi: 10.1016/j.mce.2013.05.024. Epub 2013 Jun 6.
Previous studies have indicated that AMP-activated protein kinase (AMPK) plays a critical role in the control of cardiac hypertrophy mediated by different stimuli such as thyroid hormone (TH). Although the classical effects of TH mediating cardiac hypertrophy occur by transcriptional mechanisms, recent studies have identified other responses to TH, which are more rapid and take place in seconds or minutes evidencing that TH rapidly modulates distinct signaling pathway, which might contribute to the regulation of cardiomyocyte growth. Here, we evaluated the rapid effects of TH on AMPK signaling pathway in cultured cardiomyocytes and determined the involvement of AMPK in T3-induced cardiomyocyte growth. We found for the first time that T3 rapidly activated AMPK signaling pathway. The use of small interfering RNA against AMPK resulted in increased cardiomyocyte hypertrophy while the pharmacological stimulation of AMPK attenuated this process, demonstrating that AMPK contributes to regulation of T3-induced cardiomyocyte growth.
先前的研究表明，腺苷酸活化蛋白激酶（AMPK）在不同刺激（如甲状腺激素（TH））介导的心脏肥大调控中发挥着关键作用。尽管 TH 介导心脏肥大的经典作用是通过转录机制发生的，但最近的研究已经确定了 TH 的其他反应，这些反应更快，发生在几秒钟或几分钟内，表明 TH 快速调节不同的信号通路，这可能有助于调节心肌细胞的生长。在这里，我们评估了 TH 对培养的心肌细胞中 AMPK 信号通路的快速作用，并确定了 AMPK 在 T3 诱导的心肌细胞生长中的作用。我们首次发现 T3 可快速激活 AMPK 信号通路。使用针对 AMPK 的小干扰 RNA 会导致心肌细胞肥大增加，而 AMPK 的药理学刺激则会减弱这一过程，这表明 AMPK 有助于调节 T3 诱导的心肌细胞生长。
