Peer-Reviewed Journal Details
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Egan, B., Carson, B. P., Garcia-Roves, P. M., Chibalin, A. V., Sarsfield, F. M., Barron, N., McCaffrey, N., Moyna, N. M., Zierath, J. R., O'Gorman, D. J.
Journal Of Physiology-London
Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor. coactivator-1 alpha mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle
Optional Fields
Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator-activated receptor. coactivator-1a (PGC-1a)-dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC-1a expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC-1a transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of. V O2peak. Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at + 0, + 3 and + 19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 +/- 4.0min; HI, 36.0 +/- 2.2min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC-1a mRNA abundance increased in an intensity-dependent manner + 3 h after exercise (LO, 3.8-fold; HI, 10.2-fold, P < 0.05). AMP-activated protein kinase (AMPK) (2.8-fold, P < 0.05) and calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen-activated protein kinase (MAPK) phosphorylation increased after both trials (similar to 2.0-fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor-2 (ATF-2), increased only after HI (2.4-fold, P < 0.05). Cyclic-AMP response element binding protein (CREB) phosphorylation was elevated at + 3 h after both trials (similar to 80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0-fold, P < 0.05). In conclusion, exercise intensity regulates PGC-1a mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF-2 and HDAC phosphorylation proposed as key intensity-dependent mediators.
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