Creatine enhances differentiation of myogenic C2C12 cells by activating both p38 and Akt/PKB pathways

Louise Deldicque, Daniel Theisen, Luc Bertrand, Peter Hespe, Louis Hue, Marc Francaux*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    85 Citations (Scopus)


    In myogenic C2C12 cells, 5 mM creatine increased the incorporation of labeled [35S]methionine into sarcoplasmic (+20%, P < 0.05) and myofibrillar proteins (+50%, P < 0.01). 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 (+1,300%, P < 0.001), troponin T (+65%, P < 0.01), and titin (+40%, P < 0.05) was enhanced by creatine. Mannitol, taurine, and β-alanine did not mimic the effect of creatine, ruling out an osmolarity-dependent mechanism. The addition of rapamycin, the inhibitor of mammalian target of rapamycin/70-kDa ribosomal S6 protein kinase (mTOR/p70s6k) pathway, and SB 202190, the inhibitor of p38, completely blocked differentiation in control cells, and creatine did not reverse this inhibition, suggesting that the mTOR/p70 s6k and p38 pathways could be potentially involved in the effect induced by creatine on differentiation. Creatine upregulated phosphorylation of protein kinase B (Akt/PKB; +60%, P < 0.001), glycogen synthase kinase-3 (+70%, P < 0.001), and p70s6k (+50%, P < 0.001). Creatine also affected the phosphorylation state of p38 (-50% at 24 h and +70% at 96 h, P < 0.05) as well as the nuclear content of its downstream targets myocyte enhancer factor-2 (-55% at 48 h and +170% at 96 h, P < 0.05) and MyoD (+60%, P < 0.01). In conclusion, this study points out the involvement of the p38 and the Akt/PKB-p70s6k pathways in the enhanced differentiation induced by creatine in C2C12 cells.

    Original languageEnglish
    Pages (from-to)C1263-C1271
    JournalAmerican Journal of Physiology - Cell Physiology
    Issue number4
    Publication statusPublished - Oct 2007


    • 70-kDa ribosomal S6 protein kinase
    • Extracellular signal-regulated kinase 1/2
    • Insulin-like growth factor
    • Mitogen-activated protein kinase
    • Protein synthesis


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