MEF2A Binding to the Glut4 Promoter Occurs via an AMPK alpha(2)-Dependent Mechanism

作者：Gong, Haojie; Xie, Jin; Zhang, Nan; Yao, Lu; Zhang, Ying^*

来源：Medicine and Science in Sports and Exercise, 2011, 43(8): 1441-1450.

DOI：10.1249/MSS.0b013e31820f6093

• MEF2A NUCLEUS TRANSLOCATION
• NUCLEAR HDAC5 ASSOCIATION WITH MEF2
• HDAC5 NUCLEAR EXPORT
• GLUT4 EXPRESSION

GONG, H., J. XIE, N. ZHANG, L. YAO, and Y. ZHANG. MEF2A Binding to the Glut4 Promoter Occurs via an AMPK alpha(2)-Dependent Mechanism. Med. Sci. Sports Exerc., Vol. 43, No. 8, pp. 1441-1450, 2011. Purpose: The role of AMP-activated protein kinase alpha(2) (AMPK alpha(2)) 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 AMPK alpha(2) overexpression (OE) mice, AMPK alpha(2) knockout (KO) mice, and corresponding wild-type (WT) mice that had undertaken a 28-d program of treadmill training by: 1) AMPK alpha-Thr(172) 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 AMPK alpha(2) isoform heightened or attenuated the training-induced increase in nuclear MEF2A content, Glut4 promoter-bound MEF2A. However, OE or KO of the AMPK alpha 2 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 alpha(2)-OE training muscles. Lastly, OE of the alpha(2)-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 alpha(2)-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 AMPK alpha(2)-dependent mechanism, but intracellular signaling molecules other than AMPK alpha(2) are important in regulating training-induced HDAC5 nuclear export. Furthermore, although AMPK alpha(2) mediates the training-induced increase in Glut4 promoter-bound MEF2A, the present data do not support an essential role of AMPK alpha(2) in regulating training-induced GLUT4 expression in skeletal muscle.

• 出版日期2011-8
• 单位北京体育大学