Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production

• Published in: Journal of muscle research and cell motility Vol. 27; no. 8; pp. 577 - 584
• Main Authors: Long, Jodi H D, Lira, Vitor A, Soltow, Quinlyn A, Betters, Jenna L, Sellman, Jeff E, Criswell, David S
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01-11-2006
• Subjects: Animals; Arginine - pharmacology; Calcium Channels - metabolism; Cell Differentiation; Cell Line; Histocytochemistry; Membrane Fusion - drug effects; Mice; Myoblasts, Skeletal - cytology; Myoblasts, Skeletal - drug effects; Myoblasts, Skeletal - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitrates - analysis; Nitric oxide; Nitric Oxide - biosynthesis; Nitrites - analysis; RNA, Messenger - metabolism; Time Factors; TRPV Cation Channels - metabolism
• ISSN: 0142-4319; 1573-2657
• DOI: 10.1007/s10974-006-9078-1

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. C(2)C(12) 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.