Decrease in Akt/PKB signalling in human skeletal muscle by resistance exercise

Abstract

We analysed the effects of resistance exercise upon the phosphorylation state of proteins associated with adaptive processes from the Akt/PKB (protein kinase B) and the mitogen-activated protein kinase (MAPK) pathways. Nine healthy young men (21.7 +/- 0.55 year) performed 10 sets of 10 leg extensions at 80% of their 1-RM (repetition maximum). Muscle biopsies were taken from the vastus lateralis at rest, within the first 30 s after exercise and at 24 h post-exercise. Immediately post exercise, the phosphorylation states of Akt/PKB on Thr308 and Ser473 and 4E-BP1 on Thr37/46 (eukaryotic initiation factor 4E-binding protein 1) were decreased (-60 to -90%, P < 0.05). Conversely, the phosphorylation of p70(s6k) (p70 ribosomal S6 kinase) on Thr421/Ser424 was increased more than 20-fold (P < 0.05), and this was associated with a 10- to 50-fold increase in the phosphorylation of p38 and ERK1/2 (extracellular signal-regulated kinase) (P < 0.05). Twenty-four hours post-exercise the phosphorylation state of Akt/PKB on Thr308 was depressed, whereas the phosphorylation of p70(s6k) on Thr421/Ser424 and sarcoplasmic ERK1/2 were elevated. The present results indicate that high-intensity resistance exercise in the fasted state inhibits Akt/PKB and 4E-BP1 whilst concomitantly augmenting MAPK signalling and p70(s6k) on Thr421/Ser424.

Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men

“…This supports a recent finding in humans with a slightly different time scale and nutrients (30). An RE bout per se has also previously decreased the phosphorylation of 4E-BP1 shortly after exercise when protein or amino acids are not supplemented (8,9,30,36). Prevention of the dephosphorylation of 4E-BP1 after a bout of RE by ingestion of whey proteins probably prevents association of the 4E-BP1 with eIF4E (43).…”

“…In contrast to the rapid changes, the RE bout itself did not seem to have a consistent effect on the phosphorylation of the mTOR pathway proteins at 48 h post-RE or after a longer term RT, supporting recent human studies investigating time points 48 h (36) and 24 h post-RE (8,36), and ϳ4 days after a RT period (34,59). The only long-lasting effect of protein ingestion was the increased phosphorylation of mTOR, which remained increased in the protein group from 1 to 48 h after the RE bout and also after 21 wk of RT.…”

mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle

“…Previous studies showed elevated 4E-BP1 phosphorylation after resistance exercise (4,38). However, changes in phosphorylation of 4E-BP1 and p70S6K in response to a bout of exercise do not necessarily correspond, and some previous studies have failed to find elevated phosphorylation of 4E-BP1 (9,10,23,29). We also did not detect an elevated rate of 4E-BP1 phosphorylation 24 h after exercise throughout the training and detraining periods, suggesting differential regulation of 4E-BP1 and p70S6K.…”

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

“…Consistent with previous data in vivo (16), the hypoxia-induced depression of mTOR signaling did not significantly influence 4E-BP1 activity. The elongation factor eEF2, is shown to be controlled by P70 S6K through eEF2 kinase (13) and inhibited by AMPK (23). The lack of change in AMPK phosphorylation in hypoxic rats suggests that the increased proportion of phosphorylated eEF2, and then decreased eEF2 activity in OvH muscles at day 5 could be rather explained by the impairment of P70 S6K activation.…”