Irrcher Isabella, Walkinshaw Donald R, Sheehan Treacey E, Hood David A
Department of Biology, York University, Toronto, Ontario, Canada.
J Appl Physiol (1985). 2008 Jan;104(1):178-85. doi: 10.1152/japplphysiol.00643.2007. Epub 2007 Oct 25.
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.
甲状腺激素（T3）调节体内许多组织的功能。T3的作用主要归因于甲状腺激素受体依赖性基因转录的调节。然而，T3通过启动信号事件产生的非基因组作用正在多种细胞类型中显现出来。本研究调查了短期T3处理对大鼠体内组织中信号蛋白磷酸化从而激活信号蛋白的能力。所研究的激酶包括p38、AMP激活的蛋白激酶（AMPK）和细胞外信号调节激酶（ERK）1/2。T3处理2小时后，慢肌比目鱼肌和快肌趾长伸肌中的p38和AMPK磷酸化均增加。相比之下，两种肌肉类型中的ERK1/2均未被激活。心脏中的p38和AMPK均未受影响。然而，肝脏中的AMPK激活被T3降低。心脏中的ERK1/2激活被T3降低，但在肝脏中增加。通过测量环磷酸腺苷反应元件结合蛋白（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T3诱导的激酶磷酸化可能产生的下游后果。T3未改变与环磷酸腺苷或甲状腺激素反应元件结合的蛋白质DNA。然而，比目鱼肌在T3处理12小时后，过氧化物酶体增殖物激活受体α共激活因子-1 mRNA表达增加。这些数据首次描述了T3处理对体内激酶磷酸化的影响。我们表明，T3以组织特异性方式快速改变激酶活性。此外，T3在慢肌和快肌骨骼肌中诱导的p38和AMPK磷酸化表明，这些事件可能在介导激素诱导的骨骼肌线粒体生物发生增加中起重要作用。
