title: Independent AMP and NAD signaling regulates C2C12 differentiation and metabolic adaptation.
abstract: The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling. AICAR showed no effect on NAD pool or nampt expression but significantly reduced histone H3 acetylation and GLUT1, cytochrome C oxidase subunit 2 (COX2), and MYH3 expression. In contrast, NMN supplementation for 24 h increased NAD pool by 45 % but did not reduce histone H3 acetylation nor promote mitochondrial gene expression. The combination of AMP and NAD signaling did not induce further metabolic adaptation, but NMN ameliorated AICAR-induced myotube reduction. We interpret these results as indication that AMP and NAD contribute to C2C12 differentiation and metabolic adaptation independently.
authors.affiliation: School of Applied Physiology, Georgia Institute of Technology, 555 14th St NW, Atlanta, GA, 30332-0356, USA.
authors.forename: Chia George
authors.initials: CG
authors.lastname: Hsu
authors.affiliation: School of Applied Physiology, Georgia Institute of Technology, 555 14th St NW, Atlanta, GA, 30332-0356, USA. thomas.burkholder@hps.gatech.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Burkholder
mesh_terms: D000107:Acetylation; D000222:Adaptation, Physiological; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009537:Nicotinamide Mononucleotide / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D006657:Histones; D012265:Ribonucleotides; C495678:Slc2a1 protein, mouse; D009243:NAD; D009537:Nicotinamide Mononucleotide; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D018995:Myosin Heavy Chains; C031143:AICA ribonucleotide
keywords: ATP production; C2C12 myotubes; Metabolite signaling; Nicotinamide mononucleotide