title: Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production.
abstract: 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.
authors.affiliation: Center for Exercise Science, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Jodi H D
authors.initials: JH
authors.lastname: Long
authors.forename: Vitor A
authors.initials: VA
authors.lastname: Lira
authors.forename: Quinlyn A
authors.initials: QA
authors.lastname: Soltow
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Betters
authors.forename: Jeff E
authors.initials: JE
authors.lastname: Sellman
authors.forename: David S
authors.initials: DS
authors.lastname: Criswell
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D006651:Histocytochemistry; D008561:Membrane Fusion / Q000187:drug effects*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C446923:Trpv6 protein, mouse; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester