High-intensity muscle contraction-mediated increases in Akt1 and Akt2 phosphorylation do not contribute to mTORC1 activation and muscle protein synthesis

High-intensity muscle contraction (HiMC) is known to induce muscle protein synthesis, a process in which mechanistic target of rapamycin (mTOR) is reported to play a critical role. However, the mechanistic details have not been completely elucidated. Here, we investigated whether Akt plays a role in...

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Bibliographic Details
Published in:Journal of applied physiology (1985) 2020-04, Vol.128 (4), p.830-837
Main Authors: Maruyama, Yuki, Ikeda, Chisaki, Wakabayashi, Koki, Ato, Satoru, Ogasawara, Riki
Format: Article
Language:English
Subjects:
Activation
Adrenal glands
AKT protein
AKT1 protein
AKT2 protein
Animals
Electrical stimuli
Enzyme inhibitors
Gastrocnemius muscle
Kinases
Male
Mechanistic Target of Rapamycin Complex 1 - metabolism
Mice
Mice, Inbred C57BL
Muscle Contraction
Muscle Proteins - biosynthesis
Muscle, Skeletal - metabolism
Muscles
Muscular function
Phosphorylation
Protein biosynthesis
Protein synthesis
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Rapamycin
Signal Transduction
TOR protein
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Summary:High-intensity muscle contraction (HiMC) is known to induce muscle protein synthesis, a process in which mechanistic target of rapamycin (mTOR) is reported to play a critical role. However, the mechanistic details have not been completely elucidated. Here, we investigated whether Akt plays a role in regulating HiMC-induced mTORC1 activation and muscle protein synthesis using a rodent model of resistance exercise and MK2206 (an Akt kinase inhibitor). The right gastrocnemius muscle of male C57BL/6J mice aged 10 wk was isometrically contracted via percutaneous electrical stimulation (100 Hz, 5 sets of 10 3-s contractions, 7-s rest between contractions, and 3-min rest between sets), while the left gastrocnemius muscle served as a control. Vehicle or MK2206 was injected intraperitoneally 6 h before contraction. MK2206 inhibited both resting and HiMC-induced phosphorylation of Akt1 Ser-473 and Akt2 Ser-474. MK2206 also inhibited the resting phosphorylation of p70S6K and 4E-BP1, which are downstream targets of mTORC1; however, it did not inhibit the HiMC-induced increase in phosphorylation of these targets. Similarly, MK2206 inhibited the resting muscle protein synthesis, but not the resistance exercise-induced muscle protein synthesis. On the basis of these observations, we conclude that although Akt2 regulates resting mTORC1 activity and muscle protein synthesis, HiMC-induced increases in mTORC1 activity and muscle protein synthesis are Akt-independent processes. Akt is well known to be an upstream regulator of mechanistic target of rapamycin (mTOR) and has three isoforms in mammals, namely, Akt1, Akt2, and Akt3. We found that high-intensity muscle contraction (HiMC) increases Akt1 and Akt2 phosphorylation; however, HiMC-induced increases in mTORC1 activity and muscle protein synthesis are Akt-independent processes.
ISSN:8750-7587
1522-1601
DOI:10.1152/JAPPLPHYSIOL.00578.2019