title: Effects of creatine and its analog, β-guanidinopropionic acid, on the differentiation of and nucleoli in myoblasts.
abstract: The effects of supplementation with creatine (Cr) and its analog, β-guanidinopropionic acid (β-GPA), on the differentiation of myoblasts and the numbers of nucleoli were studied in C2C12 cells. The cells were cultured in differentiation medium for 4 d. Then Cr (1 mM) or β-GPA (1 mM) was added to the cells, and the mixture was cultured for an additional 2 d. Although the number of myotubes was not different among the groups, myotube diameters and nuclear numbers in myotubes were increased by Cr and β-GPA treatment respectively. The expression of differentiation marker proteins, myogenin, and the myosine heavy chain, was increased in the β-GPA group. Supplementation with β-GPA also increased the percentage of p21 (inhibitor for cell cycle progression)-positive myoblasts. Supplementation with Cr inhibited the decrease in nucleoli numbers, whereas β-GPA increased nucleolar sizes in the myotubes. These results suggest that β-GPA supplementation stimulated the differentiation of myoblasts into multi-nucleated myotubes through induction of p21 expression.
authors.affiliation: Department of Health and Sports Sciences, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kawano
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ogura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Higo
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohira
authors.forename: Masahiro
authors.initials: M
authors.lastname: Terada
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Oke
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002466:Cell Nucleolus / Q000187:drug effects; D003401:Creatine / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis* / Q000096:biosynthesis; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008856:Microscopy, Fluorescence; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018008:Myogenin / Q000032:analysis / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000032:analysis / Q000096:biosynthesis; D011422:Propionates / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006146:Guanidines; D018008:Myogenin; D011422:Propionates; D018995:Myosin Heavy Chains; D003401:Creatine; C005775:guanidinopropionic acid