Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo
Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo
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DOI：
10.1152/japplphysiol.00643.2007
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Hood, David A.
中科院分区：
文献类型：
--
作者：
Irrcher, Isabella;Walkinshaw, Donald R.;Hood, David A.
甲状腺激素（T-3）调节体内许多组织的功能。T-3的作用在很大程度上归因于甲状腺激素受体依赖性基因转录的调节。然而，T-3通过启动信号事件的非基因组作用正在许多细胞类型中出现。本研究调查了短期T-3治疗磷酸化的能力，因此，激活体内大鼠组织中的信号蛋白。研究的激酶包括p38、AMP活化蛋白激酶（AMPK）和细胞外信号调节激酶（ERK）1/2。2小时的T-3治疗后，p38和AMPK磷酸化增加慢收缩比目鱼肌和快收缩跖肌。相反，ERK 1/2在两种肌肉类型中均未被激活。心脏中p38和AMPK均未受影响。而肝脏AMPK活性则被T-3抑制。T-3可降低心脏ERK 1/2的激活，但可增加肝脏ERK 1/2的激活。通过测量cAMP反应元件结合蛋白（CREB）和甲状腺激素受体DNA结合，以及过氧化物酶体增殖物激活受体α共激活因子-1 mRNA水平，研究了T-3诱导的激酶磷酸化的可能下游后果。蛋白质DNA结合cAMP或甲状腺激素反应元件未被T-3改变。然而，过氧化物酶体增殖物激活受体-α共激活因子-1 mRNA的表达增加后12小时的T-3治疗比目鱼肌。这些数据是第一个表征T-3治疗对体内激酶磷酸化的影响。我们表明，T-3迅速修改激酶活性的组织特异性的方式。此外，T-3诱导的磷酸化p38和AMPK在慢肌和快肌骨骼肌表明，这些事件可能是重要的，在介导骨骼肌线粒体生物合成的增加。
Thyroid hormone (T-3) regulates the function of many tissues within the body. The effects of T-3 have largely been attributed to the modulation of thyroid hormone receptor-dependent gene transcription. However, nongenomic actions of T-3 via the initiation of signaling events are emerging in a number of cell types. This study investigated the ability of short-term T-3 treatment to phosphorylate and, therefore, activate signaling proteins in rat tissues in vivo. The kinases investigated included p38, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) 1/2. Following 2 h of T-3 treatment, p38 and AMPK phosphorylation was increased in both the slow-twitch soleus and the fast-twitch plantaris muscles. In contrast, ERK1/2 was not activated in either muscle type. Neither p38 nor AMPK was affected in heart. However, AMPK activation was decreased by T-3 in liver. ERK1/2 activation was decreased by T-3 in heart, but increased in liver. Possible downstream consequences of T-3-induced kinase phosphorylation were investigated by measuring cAMP response element binding protein (CREB) and thyroid hormone receptor DNA binding, as well as peroxisome proliferator-activated receptor-alpha coactivator-1 mRNA levels. Protein DNA binding to the cAMP or thyroid hormone response elements was unaltered by T-3. However, peroxisome proliferator-activated receptor-alpha coactivator-1 mRNA expression was increased following 12 h of T-3 treatment in soleus. These data are the first to characterize the effects of T-3 treatment on kinase phosphorylation in vivo. We show that T-3 rapidly modifies kinase activity in a tissue-specific fashion. Moreover, the T-3-induced phosphorylation of p38 and AMPK in both slow- and fast-twitch skeletal muscles suggests that these events may be important in mediating hormone-induced increases in mitochondrial biogenesis in skeletal muscle.