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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/E408    most recent 00403.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Vissing, K. Articles by Kiens, B. Search for Related Content PubMed PubMed Citation Articles by Vissing, K. Articles by Kiens, B.

Effect of sex differences on human MEF2 regulation during endurance exercise

¹Department of Sport Science, University of Aarhus, Aarhus, Denmark; ²Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia; ³The Copenhagen Muscle Research Center, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen; ⁴The Copenhagen Muscle Research Center, Department of Molecular Muscle Biology, Rigshospitalet, Copenhagen; and ⁵Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Submitted 26 June 2007 ; accepted in final form 21 November 2007

Women exhibit an enhanced capability for lipid metabolism during endurance exercise compared with men. The underlying regulatory mechanisms behind this sex-related difference are not well understood but may comprise signaling through a myocyte enhancer factor 2 (MEF2) regulatory pathway. The primary purpose of this study, therefore, was to investigate the protein signaling of MEF2 regulatory pathway components at rest and during 90 min of bicycling exercise at 60% O_2peak in healthy, moderately trained men (n = 8) and women (n = 9) to elucidate the potential role of these proteins in substrate utilization during exercise. A secondary purpose was to screen for mRNA expression of MEF2 isoforms and myogenic regulatory factor (MRF) family members of transcription factors at rest and during exercise. Muscle biopsies were obtained before and immediately after exercise. Nuclear AMP-activated protein kinase- (AMPK) Thr¹⁷² (P < 0.001), histone deacetylase 5 (HDAC5) Ser⁴⁹⁸ (P < 0.001), and MEF2 Thr (P < 0.01) phosphorylation increased with exercise. No significant sex differences were observed at rest or during exercise. At rest, no significant sex differences were observed in mRNA expression of the measured transcription factors. mRNA for transcription factors MyoD, myogenin, MRF4, MEF2A, MEF2C, MEF2D, and peroxisome proliferator-activated receptor- coactivator 1 (PGC1) were significantly upregulated by exercise. Of these, MEF2A mRNA increased 25% specifically in women (P < 0.05), whereas MEF2D mRNA tended to increase in men (P = 0.11). Although minor sex differences in mRNA expression were observed, the main finding of the present study was the implication of a joint signaling action of AMPK, HDAC5, and PGC1 on MEF2 in the immediate regulatory response to endurance exercise. This signaling response was independent of sex.

skeletal muscle; myogenic regulatory factor; AMP-activated protein kinase; histone deacetylase 5; peroxisome proliferator-activated receptor- coactivator 1