Premium
AMP‐activated protein kinase enhances myogenin expression and myogenesis
Author(s) -
Fu Xing,
Zhao Junxing,
Zhu MeiJun,
Du Min
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.939.10
Subject(s) - myogenin , ampk , myogenesis , c2c12 , myocyte , protein kinase a , amp activated protein kinase , chemistry , gene knockdown , microbiology and biotechnology , phosphorylation , biology , biochemistry , apoptosis
AMP‐activated protein kinase (AMPK) is a master regulator of energy metabolism. We previously demonstrated that AMPK activity is correlated with skeletal muscle development, but the underlying mechanisms are unclear. Myogenin regulates myoblast fusion, a critical step of myogenesis. We hypothesized that AMPK regulates myogenesis through controlling myogenin expression. In C2C12 cells, AMPKα1 but not AMPKα2 knockdown by shRNA down‐regulated myogenin mRNA expression and its protein content, as well as myosin heavy chain (MHC) protein content. AMPKα1 knockout (KO) primary myoblasts but not AMPKα2 KO myoblasts showed reduced myogenin expression and reduced MHC protein content as compared to wild‐type (WT) myoblasts. AMPKα1 was found to be expressed at a much higher level than AMPKα2 in myoblasts. AMPK activation by AICAR promoted myogenin expression in WT, AMPKα1 KO, and AMPKα2 KO primary myoblasts. Histone deacetylase (HDAC) 5 knockdown by shRNA increased myogenin mRNA and protein contents, together with enhanced MHC expression and myotube formation in C2C12 cells. Mutation of two phosphorylation sites in HDAC5, Ser 259 and 498, abolished the regulatory role of AMPK on myogenin expression in both C2C12 cells and primary myoblasts. In conclusion, AMPK activity promotes myotube formation through enhancing myogenin expression, which is mainly mediated by AMPKα1 via HDAC5 phosphorylation. NIH R01HD067449