title: Leucine limitation regulates myf5 and myoD expression and inhibits myoblast differentiation.
abstract: Satellite cells are the major pool of muscle stem cells after birth; they represent an important component required to maintain muscle mass and functionality during life. The molecular mechanisms involved in myogenic differentiation are relatively well-known. However, the role of extracellular stimulus in the control of differentiation remains largely unresolved. Notably little is known about the impact of nutrients on this process. Here we have studied the role of leucine, an essential amino acid, in the control of myogenic differentiation. Leucine is a well-known regulator of muscle protein synthesis. It acts not only as a substrate for translation but also as a regulator of gene expression and signaling pathways such as those involving mTOR and GCN2. In this study we demonstrated that the lack of leucine abolishes the differentiation of both C2C12 myoblasts and primary satellite cells. This effect is associated with a modification of the pattern of expression of the myogenic regulatory factors (MRF) myf5 and myoD. We report an up-regulation of myf5 mRNA and a decrease of myoD protein level during leucine starvation. This study demonstrates the importance of a nutrient, leucine, in the control of the myogenic differentiation program.
authors.affiliation: Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 CLERMONT-FERRAND, France. julien.averous@clermont.inra.fr
authors.forename: J
authors.initials: J
authors.lastname: Averous
authors.forename: J C
authors.initials: JC
authors.lastname: Gabillard
authors.forename: I
authors.initials: I
authors.lastname: Seiliez
authors.forename: D
authors.initials: D
authors.lastname: Dardevet
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007930:Leucine / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases; D007930:Leucine