RGD Reference Report - Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1alpha in rat muscle. - Rat Genome Database

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Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1alpha in rat muscle.

Authors: Branvold, DJ  Allred, DR  Beckstead, DJ  Kim, HJ  Fillmore, N  Condon, BM  Brown, JD  Sudweeks, SN  Thomson, DM  Winder, WW 
Citation: Branvold DJ, etal., J Appl Physiol (1985). 2008 Oct;105(4):1218-27. doi: 10.1152/japplphysiol.00997.2007. Epub 2008 Jul 31.
RGD ID: 10059691
Pubmed: PMID:18669938   (View Abstract at PubMed)
DOI: DOI:10.1152/japplphysiol.00997.2007   (Journal Full-text)

Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in skeletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB1. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB1, along with binding partner proteins. LKB1, MO25, 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 0.01% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB1 and MO25 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB1 responses were variable, but MO25 increased in all. In soleus, MO25 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 phospho-cAMP 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 proliferator-activated receptor-gamma coactivator-1alpha, 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 LKB1 and MO25 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hyperthyroidism  ISOCab39 (Rattus norvegicus)10059691; 10059691mRNA and protein:increased expression:muscle:RGD 
hyperthyroidism  IEP 10059691; 10059691mRNA and protein:increased expression:muscle:RGD 
hyperthyroidism  ISOPpargc1a (Rattus norvegicus)10059691; 10059691protein:increased expression:soleus muscle (rat)RGD 
hyperthyroidism  IEP 10059691protein:increased expression:soleus muscle (rat)RGD 
hyperthyroidism  ISOStk11 (Rattus norvegicus)10059691; 10059691mRNA and protein:increased expression:muscle:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to thyroid hormone  IEP 10059691; 10059691 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cab39  (calcium binding protein 39)
Ppargc1a  (PPARG coactivator 1 alpha)
Stk11  (serine/threonine kinase 11)

Genes (Mus musculus)
Cab39  (calcium binding protein 39)
Ppargc1a  (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha)
Stk11  (serine/threonine kinase 11)

Genes (Homo sapiens)
CAB39  (calcium binding protein 39)
PPARGC1A  (PPARG coactivator 1 alpha)
STK11  (serine/threonine kinase 11)


Additional Information