Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo.
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.
Irrcher
Isabella
I
Department of Biology, York University, Toronto, Ontario, Canada.
Walkinshaw
Donald R
DR
Sheehan
Treacey E
TE
Hood
David A
DA
D055372:AMP-Activated Protein Kinases; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D007274:Injections, Intraperitoneal; D008099:Liver / Q000201:enzymology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014284:Triiodothyronine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D009097:Multienzyme Complexes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D014284:Triiodothyronine; D004247:DNA; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases