A distinct AMP-activated protein kinase phosphorylation site characterizes cardiac hypertrophy induced by L-thyroxine and angiotensin II.
1. The purpose of the present study was to evaluate differences in the AMP-activated protein kinase (AMPK) phosphorylation sites in cardiac hypertrophy induced by L-thyroxine and angiotensin (Ang) II. 2. Cardiac hypertrophy was induced in wild-type and AMPKalpha2-knockout mice by treatment with 1 mg/kg, i.p., thyroxine or 1.44 mg/kg per day AngII for 14 days. The phenotype of the hypertrophy was evaluated using echocardiographic measurements and histological analyses. The phosphorylation of AMPK at alpha-Ser(485/491) and alpha-Thr(172) was determined by western blot analysis. 3. In wild-type mice, the phosphorylation of AMPKalpha-Ser(485/491) was significantly elevated in the AngII-treated group, but not in the thyroxine-treated group, compared with the vehicle control group. In contrast, the phosphorylation of AMPKalpha-Thr(172) was significantly increased by thyroxine, but not AngII, treatment compared with the vehicle control group. Furthermore, knockout of the AMPKalpha2 subunit abolished phosphorylation at the alpha-Ser(485/491) site and significantly suppressed phosphorylation at the alpha-Thr(172) site, resulting in alleviation of thyroxine- but not AngII-induced hypertrophy. 4. In conclusion, L-thyroxine and AngII induce the phosphorylation of distinct sites of AMPK in cardiac hypertrophy. Phosphorylation of AMPK alpha-Thr(172) may contribute to thyroxine-induced cardiac hypertrophy.
Jiang
Sheng-Yang
SY
Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Xu
Ming
M
Ma
Xiao-Wei
XW
Xiao
Han
H
Zhang
You-Yi
YY
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D013974:Thyroxine / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012313:RNA; D055372:AMP-Activated Protein Kinases; D013974:Thyroxine