Regulation of LKB1-STRAD-MO25 Complex Expression and Activation of AMPK in Skeletal Muscle by Thyroid Hormone

<p>AMP-activated protein kinase (AMPK), a heterotrimeric protein which serves as a metabolic master switch in skeletal muscle, is a research target for the pharmaceutical treatment and prevention of type 2 diabetes. The expression of all of the isoforms of the subunits of AMPK and AMPK activity are increased in skeletal muscle tissue of hyperthyroid rats. Activity of AMPK is regulated by an upstream kinase (AMPKK). The LKB1-STRAD-MO25 complex is a major AMPKK in skeletal muscle. This experiment was designed to determine whether the increase in AMPK activity is accompanied by a thyroid hormone-induced increase in the expression of the LKB1-STRAD-MO25 complex. LKB1-STRAD-MO25 complex protein expression was determined by Western blots in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 weeks, and in rats given 0.01% propylthiouracil (PTU) in drinking water for 4 weeks. The relative expression of LKB1, MO25, and STRAD, as well as PGC-1α, increased in the soleus of thyroid hormone treated rats vs. the controls. MO25 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC increased in response to electrical stimulation in muscles of all treatment groups, but was most markedly increased in hyperthyroid rats. Thyroid hormone treatment also increased the amount of phospho-CREB in the soleus, heart, and red quadriceps. These data provide evidence that thyroid hormone partially controls expression of the LKB1-STRAD-MO25 complex, as well the subsequent activation of AMPK.</p>

Name thesis:degree_name

MS

Grantor dc:publisher

Brigham Young University - Provo

Author dc:creator

• Branvold, Devon Jack

• AMPK
• LKB1
• CREB
• Acetyl-CoA carboyxlase
• PGC-1α
• Cell and Developmental Biology
• Physiology

Language dc:language

English

Repository record dc:identifier

https://scholarsarchive.byu.edu/etd/1407

OAI identifier oai:identifier

oai:scholarsarchive.byu.edu:etd-2406