title: AMPK activation by AICAR inhibits myogenic differentiation and myostatin expression in cattle.
abstract: AMP-activated protein kinase (AMPK) regulates metabolism in skeletal muscle, and myostatin (MSTN) negatively regulates skeletal muscle development and growth. In the present study, AMPK activation and the relationship between AMPK and MSTN during myogenic differentiation were investigated in cultures derived from bovine skeletal muscle. Myoblasts capable of forming myotubes were obtained from bovine skeletal muscle and treated with AICAR to activate AMPK, resulting in suppressed myotube formation. AICAR treatment significantly reduced the expression of MSTN mRNA during myogenic differentiation. Combined treatment with AICAR and MSTN suppressed myotube formation to a greater extent than AICAR alone. SB431542, an inhibitor of MSTN signaling, promoted myotube formation during myogenic differentiation. However, simultaneous treatment with AICAR blocked this effect of SB431542. Therefore, AMPK activation inhibits myogenic differentiation but may suppress MSTN expression to balance muscle development.
authors.affiliation: Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Miyake
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Eri
authors.initials: E
authors.lastname: Kitagawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sakurada
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D055435:Myostatin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012265:Ribonucleotides / Q000494:pharmacology*
chemical_list: D055435:Myostatin; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide