| Abstrakt: |
Branvold DJ, Allred DR, Beckstead DJ, Kim Hi, Fillmore N, Condon BM, Brown JD, Sudweeks SN, Thomson DM, Winder WW. Thyroid hormone effects on LKB1, M025, phospho-AMPK, phosphoCREB, and PGC-la in rat muscle. JAppi Physiol 105: 1218-1227, 2008. First published July 31, 2008; doi:l0.l152/japplphysiol.00997.2007.Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in ~keletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB I. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB I, along with binding partner proteins. LKB1, M025, and downstream targets were determined in muscle extracts in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 wk, and in rats given 0.0 1% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB 1 and M025 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB 1 responses were variable, but M025 increased in all. In soleus, M025 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC were elevated in soleus and gastrocnemius of hyperthyroid rats. Thyroid hormone treatment also increased the amount of phosphocAMP response element binding protein (CREB) in the soleus, heart, and red quadriceps. Four proteins having CREB response elements (CRE) in promoter regions of their genes (peroxisome proliferatoractivated receptor-γ coactivator-1α, uncoupling protein 3, cytochrome c, and hexokinase II) were all increased in soleus in response to thyroid hormones. These data provide evidence that thyroid hormones increase soleus muscle LKBI and M025 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters. [ABSTRACT FROM AUTHOR] |
