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A dynamic ribosomal biogenesis response is not required for IGF‐1–mediated hypertrophy of human primary myotubes
Author(s) -
Crossland Hannah,
Timmons James A.,
Atherton Philip J.
Publication year - 2017
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/fj.201700329r
Subject(s) - ribosome biogenesis , myogenesis , muscle hypertrophy , biology , microbiology and biotechnology , ribosomal rna , protein biosynthesis , ribosomal protein , rna , p70 s6 kinase 1 , ribosomal protein s6 , ribosome , medicine , myocyte , chemistry , endocrinology , phosphorylation , protein kinase b , biochemistry , gene
Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF‐1–mediated myotube hypertrophy in vitro. Primary skeletal myotubes were treated with IGF‐1 (50 ng/ml) with or without 0.5 μM CX‐5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre‐rRNA expression (−64 ± 5% vs . IGF‐1; P < 0.001) and total RNA content (−16 ± 2% vs. IGF‐1; P < 0.001) in IGF‐1‐treated myotubes. IGF‐1‐mediated increases in myotube diameter (1.27 ± 0.09‐fold, P < 0.05 vs . control) and total protein (+20 ± 2%; P < 0.001 vs . control) were not prevented by CX treatment. Suppression of rRNA synthesis during IGF‐1 treatment did not prevent early increases in AKT (+203 ± 39% vs . CX; P < 0.001) and p70 S6K1 (269 ± 41% vs . CX; P < 0.001) phosphorylation. Despite robust inhibition of the dynamic ribosomal biogenesis response to IGF‐1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF‐1‐induced myotube hypertrophy in vitro. —Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF‐1‐mediated hypertrophy of human primary myotubes. FASEB J. 31, 5196‐5207 (2017). www.fasebj.org