FOXO1 and GSK-3 beta Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
PLoS One
ISSN
1932-6203
EISSN
Wydawca
PUBLIC LIBRARY SCIENCE
DOI
URL
Rok publikacji
2016
Numer zeszytu
1
Strony od-do
e0146726
Numer tomu
11
Identyfikator DOI
Liczba arkuszy
2,71
Słowa kluczowe
en
Insulin
Mitochondria
Skeletal muscles
Muscle cells
Muscle differentiation
Transcription factors
Myoblasts
Myosins
Open access
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Creative Commons — Uznanie autorstwa
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Razem z publikacją
Data udostępnienia w sposób otwarty
Streszczenia
Język
en
Treść
Myogenesis and muscle hypertrophy account for muscle growth and adaptation to work overload, respectively. In adults, insulin and insulin-like growth factor 1 stimulate muscle growth, although their links with cellular energy homeostasis are not fully explained. Insulin plays critical role in the control of mitochondrial activity in skeletal muscle cells, and mitochondria are essential for insulin action. The aim of this study was to elucidate molecular mechanism(s) involved in mitochondrial control of insulin-dependent myogenesis. The effects of several metabolic inhibitors (LY294002, PD98059, SB216763, LiCl, rotenone, oligomycin) on the differentiation of C2C12 myoblasts in culture were examined in the short-term (hours) and long-term (days) experiments. Muscle cell viability and mitogenicity were monitored and confronted with the activities of selected genes and proteins expression. These indices focus on the roles of insulin, glycogen synthase kinase 3 beta (GSK-3 beta) and forkhead box protein O1 (FOXO1) on myogenesis using a combination of treatments and inhibitors. Long-term insulin (10 nM) treatment in ``normoglycemic'' conditions led to increased myogenin expression and accelerated myogenesis in C2C12 cells. Insulin-dependent myogenesis was accompanied by the rise of mtTFA, MtSSB, Mfn2, and mitochondrially encoded Cox-1 gene expressions and elevated levels of proteins which control functions of mitochondria (kinase-PKB/AKT, mitofusin 2 protein-Mfn-2). Insulin, via the phosphatidylinositol 3-kinase (PI3-K)/AKT-dependent pathway reduced transcription factor FOXO1 activity and altered GSK-3 beta phosphorylation status. Once FOXO1 and GSK-3 beta activities were inhibited the rise in Cox-1 gene action and nuclear encoded cytochrome c oxidase subunit IV (COX IV) expressions were observed, even though some mRNA and protein results varied. In contrast to SB216763, LiCl markedly elevated Mfn2 and COX IV protein expression levels when given together with insulin. Thus, inhibition of GSK-3 beta activity by insulin alone or together with LiCl raised the expression of genes and some proteins central to the metabolic activity of mitochondria resulting in higher ATP synthesis and accelerated myogenesis. The results of this study indicate that there are at least two main targets in insulin-mediated myogenesis: notably FOXO1 and GSK-3 beta both playing apparent negative role in muscle fiber formation.
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Original article
Original article presents the results of original research or experiment.
Inne
System-identifier
PBN-R:717938
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