title: Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo.
abstract: 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.
authors.affiliation: Department of Biology, York University, Toronto, Ontario, Canada.
authors.forename: Isabella
authors.initials: I
authors.lastname: Irrcher
authors.forename: Donald R
authors.initials: DR
authors.lastname: Walkinshaw
authors.forename: Treacey E
authors.initials: TE
authors.lastname: Sheehan
authors.forename: David A
authors.initials: DA
authors.lastname: Hood
mesh_terms: 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*
chemical_list: 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