Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle

Bartlett JD, Hwa Joo C, Jeong TS, Louhelainen J, Cochran AJ, Gibala MJ, Gregson W, Close GL, Drust B, Morton JP. Matched work high-intensity interval and continuous running induce similar increases in PGC-1 alpha mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. J Appl Physiol 112: 1135-1143, 2012. First published January 29, 2012; doi:10.1152/japplphysiol.01040.2011.-The aim of the present study was to test the hypothesis that acute high-intensity interval (HIT) running induces greater activation of signaling pathways associated with mitochondrial biogenesis compared with moderate-intensity continuous (CONT) running matched for work done. In a repeated-measures design, 10 active men performed two running protocols consisting of HIT [6 x 3-min at 90% maximal oxygen consumption ((V) over dot O-2max) interspersed with 3-min recovery periods at 50% (V) over dot O-2max with a 7-min warm-up and cool-down period at 70% (V) over dot O-2max] or CONT (50-min continuous running at 70% (V) over dot O-2max). Both protocols were matched, therefore, for average intensity, duration, and distance run. Muscle biopsies (vastus lateralis) were obtained preexercise, postexercise, and 3 h postexercise. Muscle glycogen decreased (P < 0.05) similarly in HIT and CONT (116 +/- 11 vs. 111 +/- 17 mmol/kg dry wt, respectively). Phosphorylation (P-) of p38MAPK(Thr180/Tyr182) (1.9 < 0.1- vs. 1.5 +/- 0.2-fold) and AMPK(Thr172) (1.5 +/- 0.3- vs. 1.5 +/- 0.1-fold) increased immediately postexercise (P < 0.05) in HIT and CONT, respectively, and returned to basal levels at 3 h postexercise. P-p53(Ser15) (HIT, 2.7 +/- 0.8-fold; CONT, 2.1 +/- 0.8-fold), PGC-1 alpha mRNA (HIT, 4.2 +/- 1.7-fold; CONT, 4.5 +/- 0.9-fold) and HSP72 mRNA (HIT, 4.4 +/- 2-fold; CONT, 3.5 +/- 1-fold) all increased 3 h postexercise (P < 0.05) although neither parameter increased (P > 0.05) immediately postexercise. There was no difference between trials for any of the above signaling or gene expression responses (P > 0.05). We provide novel data by demonstrating that acute HIT and CONT running (when matched for average intensity, duration, and work done) induces similar activation of molecular signaling pathways associated with regulation of mitochondrial biogenesis. Furthermore, this is the first report of contraction-induced p53 phosphorylation in human skeletal muscle, thus highlighting an additional pathway by which exercise may initiate mitochondrial biogenesis.