Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells.
This study compared the effects of leucine and glutamine on the mTOR pathway, on protein synthesis and on muscle-specific gene expression in myogenic C(2)C(12) cells. Leucine increased the phosphorylation state of mTOR, on both Ser2448 and Ser2481, and its downstream effectors, p70(S6k), S6 and 4E-BP1. By contrast, glutamine decreased the phosphorylation state of mTOR on Ser2448, p70(S6k) and 4E-BP1, but did not modify the phosphorylation state of mTOR on Ser2481 and S6. Whilst the phosphorylation state of the mTOR pathway is usually related to protein synthesis, the incorporation of labelled methionine/cysteine was only transiently modified by leucine and was unaltered by glutamine. However, these two amino acids affected the mRNA levels of desmin, myogenin and myosin heavy chain in a time-dependant manner. In conclusion, leucine and glutamine have opposite effects on the mTOR pathway. Moreover, they induce modification of muscle-specific gene expression, unrelated to their effects on the mTOR/p70(S6k) pathway.
Deldicque
L
L
Département d Education Physique et de Réadaptation, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Sanchez Canedo
C
C
Horman
S
S
De Potter
I
I
Bertrand
L
L
Hue
L
L
Francaux
M
M
D000818:Animals; D002460:Cell Line; D004336:Drug Antagonism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005973:Glutamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007930:Leucine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis*; D032448:Myoblasts, Skeletal; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D009124:Muscle Proteins; D005973:Glutamine; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D007930:Leucine