title: AMP-activated protein kinase stimulates myostatin expression in C2C12 cells.
abstract: AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism in skeletal muscle; AMPK induces muscle protein degradation but the underlying mechanisms are unclear. Myostatin is a powerful negative regulator of skeletal muscle mass and growth in mammalian species. We hypothesized that AMPK stimulates myostatin expression, which provides an explanation for the negative role of AMPK in muscle growth. The objective of this study is to demonstrate that AMPK stimulates myostatin expression using C2C12 cells as a model. Activation of AMPK by 5-aminoimidazole-4-carboxamide-1-β-d-riboruranoside (AICAR) dramatically increased the mRNA expression and protein content of myostatin in C2C12 myotubes, and to a lesser degree in myoblasts. Metformin, another AMPK activator, also stimulated myostatin expression at low concentrations. In addition, ectopic expression of AMPK wild-type α subunit (enhancing AMPK activity) and AMPK K45R mutant (knockdown AMPK activity) enhanced and reduced myostatin expression, respectively. These results indicate that AMPK stimulates myostatin expression in C2C12 cells, providing an explanation for the negative effect of AMPK on muscle growth.
authors.affiliation: Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Das
authors.forename: Qi-Yuan
authors.initials: QY
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Liang
authors.forename: Marcio S
authors.initials: MS
authors.lastname: Duarte
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Grant D
authors.initials: GD
authors.lastname: Trobridge
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D055435:Myostatin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012265:Ribonucleotides / Q000494:pharmacology
chemical_list: D055435:Myostatin; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide