Am J Physiol Cell Physiol. 2007 Jul 25.
Creatine enhances differentiation of myogenic C2C12 cells by activating both p38 and Akt/PKB pathways.
Deldicque L, Theisen D, Bertrand L, Hespel PJ, Hue L, Francaux M.
Institut d'Education physique et de Readaptation, Universite catholique de Louvain, Louvain-la-Neuve, Belgium.

In myogenic C2C12 cells, 5mM creatine increased the incorporation of labelled [(35)S] methionine into sarcoplasmic (+20%, P<0.05) and myofibrillar (+50%, P<0.01) proteins. Creatine also promoted the fusion of myoblasts assessed by an increased number of nuclei incorporated within myotubes (+40%, P<0.001). Expression of myosin heavy chain type II (MHC II, +1300%, P<0.001), troponin T (+65%, P<0.01) and titin (+40%, P<0.05) was enhanced by creatine. Neither mannitol, taurine, nor beta-alanine mimicked the effect of creatine, ruling out an osmolarity-dependent mechanism. The addition of rapamycin, the inhibitor of mammalian target of rapamycin/70kDa ribosomal S6 protein kinase (mTOR/p70(s6k)) pathway, and SB202190, the inhibitor of p38, completely blocked differentiation in control cells, and creatine did not reverse this inhibition, suggesting that the mTOR/p70(s6k) and the p38 pathways could be potentially involved in the effect induced by creatine on the differentiation. Creatine upregulated phosphorylation of protein kinase B (Akt/PKB, +60%, P<0.001), glycogen synthase kinase-3 (GSK-3, +70%, P<0.001) and p70(s6k) (+50%, P<0.001). Creatine also affected the phosphorylation state of p38 (-50% at 24h and +70% at 96h, P<0.05) as well as the nuclear content of its downstream targets myocyte enhancer factor-2 (MEF-2, -55% at 48h and +170% at 96h, P<0.05) and MyoD (+60%, P<0.01). In conclusion, this study points out the involvement of the p38 and the Akt/PKB-p70(s6k) pathways in the enhanced differentiation induced by creatine in C2C12 cells.

Categories: 2007, Creatine