MEF2A Binding to the Glut4 Promoter Occurs via an AMPKa2-Dependent Mechanism

• Autores: Haojie Gong, Jin Xie, Nan Zhang, Lu Yao, Ying-Dong Zhang
• Localización: Medicine & Science in Sports & exercise: Official Journal of the American College of Sports Medicine, ISSN 0195-9131, Vol. 43, Nº. 8, 2011, págs. 1441-1450
• Idioma: inglés
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• Resumen

  • Purpose: The role of AMP-activated protein kinase a2 (AMPKa2) in regulating MEF2A nucleus translocation, nuclear histone deacetylase 5 (HDAC5) association with MEF2, HDAC5 nuclear export, MEF2A binding to the Glut4 promoter, and GLUT4 expression was investigated.

    Methods: This was investigated in muscles from AMPKa2 overexpression (OE) mice, AMPKa2 knockout (KO) mice, and corresponding wild-type (WT) mice that had undertaken a 28-d program of treadmill training by: 1) AMPKa-Thr172 phosphorylation by Western blot, 2) total and nuclear MEF2A by Western blot, 3) nuclear HDAC5 association with MEF2 by coimmunoprecipitation, 4) total and nuclear HDAC5 by Western blot, 5) bound MEF2A at the Glut4 MEF2 cis-element by chromatin immunoprecipitation, and 6) GLUT4 expression by real-time polymerase chain reaction and Western blot.

    Results: OE or KO of AMPKa2 isoform heightened or attenuated the training-induced increase in nuclear MEF2A content, Glut4 promoter-bound MEF2A. However, OE or KO of the AMPKa2 isoform did not have any effect on the content of nuclear HDAC5 association with MEF2 after 28 d of exercise training, although 35% lower nuclear HDAC5 protein content was found in a2-OE training muscles. Lastly, OE of the a2-isoform was associated with 120% and 155% higher GLUT4 protein and mRNA in training muscles. However, the training-induced increases of GLUT4 protein and mRNA contents were normal in a2-KO muscles despite the reduced AMPK signaling.

    Conclusions: Exercise training increases the nuclear MEF2A content and binding of MEF2A to their binding sites on the Glut4 gene by an AMPKa2-dependent mechanism, but intracellular signaling molecules other than AMPKa2 are important in regulating training-induced HDAC5 nuclear export. Furthermore, although AMPKa2 mediates the training-induced increase in Glut4 promoter-bound MEF2A, the present data do not support an essential role of AMPKa2 in regulating training-induced GLUT4 expression in skeletal muscle.