Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production
- 249 Downloads
The semi-essential amino acid, l-arginine (l-Arg), is the substrate for endogenous synthesis of nitric oxide, a molecule that is involved in myoblast proliferation and fusion. Since l-Arg supply may limit nitric oxide synthase (NOS) activity in endothelial cells, we examined l-Arg supplementation in differentiating mouse myoblasts and tested the hypothesis that l-Arg exerts direct effects on myoblast fusion via augmentation of endogenous nitric oxide production. C2C12 myoblasts in differentiation media received one of␣the␣following treatments for 120 h: 1 mM l-Arg, 0.1 mM N-nitro-l-arginine methyl ester (l-NAME), l-Arg + l-NAME, 10 mM l-Lysine, or no supplement (Control). Cultures were fixed and stained with hematoxylin and eosin for microphotometric image analysis of myotube density, nuclear density, and fusion index (% of total nuclei in myotubes). Endogenous production of nitric oxide during the treatment period peaked between 24 and 48 h. l-Arg amplified nitric oxide production between 0 and 24 h and increased myotube density, total nuclei number, and nuclear fusion index. These l-Arg effects were prevented by the NOS inhibitor, l-NAME. Further, l-Lysine, a competitive inhibitor of l-Arg uptake, repressed nitric oxide production and reduced myotube density and fusion index. In summary, l-Arg augments myotube formation and increases nitric oxide production in a process limited by cellular l-Arg uptake.
KeywordsC2C12 myotubes L-NAME Skeletal muscle Differentiation
Unable to display preview. Download preview PDF.
Funded by the University of Florida Research Opportunity Fund (DSC).
- Baydoun AR, Wileman SM, Wheeler-Jones CPD, Marber MS, Mann GE, Pearson JD, Closs EI (1999) Transmembrane signaling mechanisms regulating expression of cationic amino acid transporters and inducible nitric oxide synthase in rat vascular smooth muscle cells. Biochem J 344:265–272PubMedCrossRefGoogle Scholar
- Wu G, Morris SM (1998) Arginine maetabolism: nitric oxide and beyond. Biochm J 336:1–17Google Scholar