mVps34 is activated following high-resistance contractions.
Following resistance exercise in the fasted state, both protein synthesis and degradation in skeletal muscle are increased. The addition of essential amino acids potentiates the synthetic response suggesting that an amino acid sensor, which is involved in both synthesis and degradation, may be activated by resistance exercise. One such candidate protein is the class 3 phosphatidylinositol 3OH-kinase (PI3K) Vps34. To determine whether mammalian Vps34 (mVps34) is modulated by high-resistance contractions, mVps34 and S6K1 (an index of mTORC1) activity were measured in the distal hindlimb muscles of rats 0.5, 3, 6 and 18 h after acute unilateral high-resistance contractions with the contralateral muscles serving as a control. In the lengthening tibialis anterior (TA) muscle, S6K1 (0.5 h = 366.3 +/- 112.08%, 3 h = 124.7 +/- 15.96% and 6 h = 129.2 +/- 0%) and mVps34 (3 h = 68.8 +/- 15.1% and 6 h = 36.0 +/- 8.79%) activity both increased, whereas in the shortening soleus and plantaris (PLN) muscles the increase was significantly lower (PLN S6K1 0.5 h = 33.1 +/- 2.29% and 3 h = 47.0 +/- 6.65%; mVps34 3 h = 24.5 +/- 7.92%). HPLC analysis of the TA demonstrated a 25% increase in intramuscular leucine concentration in rats 1.5 h after exercise. A similar level of leucine added to C2C12 cells in vitro increased mVps34 activity 3.2-fold. These data suggest that, following high-resistance contractions, mVps34 activity is stimulated by an influx of essential amino acids such as leucine and this may prolong mTORC1 signalling and contribute to muscle hypertrophy.
MacKenzie
Matthew G
MG
James Black Centre, University of Dundee, Dundee, DD1 5EH, UK.
Hamilton
D Lee
DL
Murray
James T
JT
Taylor
Peter M
PM
Baar
Keith
K
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D005260:Female; D006984:Hypertrophy; D007930:Leucine / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D005082:Physical Exertion / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D055070:Resistance Training; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism
D007930:Leucine; D019869:Phosphatidylinositol 3-Kinases; D019893:Ribosomal Protein S6 Kinases; D014157:Transcription Factors; C519510:Crtc1 protein, rat; C526901:Rps6kb1 protein, rat