Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle

McGee, Sean and Hargreaves, Mark 2004, Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle, Diabetes, vol. 53, pp. 1208-1214.

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Title Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle
Author(s) McGee, Sean
Hargreaves, Mark
Journal name Diabetes
Volume number 53
Start page 1208
End page 1214
Publisher American Diabetes Association
Place of publication New York, N.Y.
Publication date 2004-05
ISSN 0012-1797
1939-327X
Summary Overexpression of GLUT4 in skeletal muscle enhances whole-body insulin action. Exercise increases GLUT4 gene and protein expression, and a binding site for the myocyte enhancer factor 2 (MEF-2) is required on the GLUT4 promoter for this response. However, the molecular mechanisms involved remain elusive. In various cell systems, MEF-2 regulation is a balance between transcriptional repression by histone deacetylases (HDACs) and transcriptional activation by the nuclear factor of activated T-cells (NFAT), peroxisome proliferator-activated receptor- coactivator 1 (PGC-1), and the p38 mitogen-activated protein kinase. The purpose of this study was to determine if these same mechanisms regulate MEF-2 in contracting human skeletal muscle. Seven subjects performed 60 min of cycling at 70% of Vo2peak. After exercise, HDAC5 was dissociated from MEF-2 and exported from the nucleus, whereas nuclear PGC-1 was associated with MEF-2. Exercise increased total and nuclear p38 phosphorylation and association with MEF-2, without changes in total or nuclear p38 protein abundance. This result was associated with p38 sequence-specific phosphorylation of MEF-2 and an increase in GLUT4 mRNA. Finally, we found no role for NFAT in MEF-2 regulation. From these data, it appears that HDAC5, PGC-1, and p38 regulate MEF-2 and could be potential targets for modulating GLUT4 expression.
Language eng
Field of Research 060104 Cell Metabolism
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2004, American Diabetes Association
Persistent URL http://hdl.handle.net/10536/DRO/DU:30002434

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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