EXERCISE AND CLASS IIa HISTONE DEACETYLASES IN HUMAN SKELETAL MUSCLE

Abstract

The class IIa histone deacetylases (HDACs) are involved in the regulation of skeletal muscle phenotype via effects on myocyte enhancer factor 2 (MEF2) transcriptional activity. We have previously shown that a single exercise bout reduces nuclear HDAC5 abundance and MEF2‐HDAC5 association, with a concomitant increase in GLUT4 mRNA, in human skeletal muscle (McGee & Hargreaves. Diabetes. 53:1208–1214, 2004). In the present study, we obtained muscle (v. lateralis) samples from nine untrained men (23 ± 1 yr, 75 ± 6 kg) before and after exercise (60 min, 77 ± 2% peak pulmonary oxygen uptake) to examine exercise effects on other class IIa HDACs. There was a 40% reduction (P<0.05) in nuclear HDAC4 after exercise, while nuclear HDAC5 was reduced (P<0.05) by 13%, with no changes in total HDAC4 or HDAC5 expression. There were no changes in nuclear HDAC7 or HDAC9 abundance with exercise, nor was there a change in acetyl‐H3 (K9/K14) with exercise (1.16 ± 0.15 vs. 1.0 ± 0.0 arb. units). These results suggest that nuclear‐cytosolic shuttling of HDAC4 and HDAC5, but not HDAC7 and HDAC9, could play a role in the exercise‐induced changes in skeletal muscle gene expression.