title: MEF2A binding to the Glut4 promoter occurs via an AMPKα2-dependent mechanism.
abstract: OBJECTIVE
  The role of AMP-activated protein kinase α2 (AMPKα2) 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 AMPKα2 overexpression (OE) mice, AMPKα2 knockout (KO) mice, and corresponding wild-type (WT) mice that had undertaken a 28-d program of treadmill training by: 1) AMPKα-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 AMPKα2 isoform heightened or attenuated the training-induced increase in nuclear MEF2A content, Glut4 promoter-bound MEF2A. However, OE or KO of the AMPKα2 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 α2-OE training muscles. Lastly, OE of the α2-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 α2-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 AMPKα2-dependent mechanism, but intracellular signaling molecules other than AMPKα2 are important in regulating training-induced HDAC5 nuclear export. Furthermore, although AMPKα2 mediates the training-induced increase in Glut4 promoter-bound MEF2A, the present data do not support an essential role of AMPKα2 in regulating training-induced GLUT4 expression in skeletal muscle.
authors.affiliation: Beijing Sport University, Beijing, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Gong
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Yao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015444:Exercise / Q000502:physiology; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic
chemical_list: D051275:Glucose Transporter Type 4; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; C495693:Slc2a4 protein, mouse; C534978:Prkaa2 protein, mouse; C526181:PRKAA2 protein, human; D055372:AMP-Activated Protein Kinases; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases