期刊
FASEB JOURNAL
卷 31, 期 12, 页码 5196-5207出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201700329R
关键词
RNA; skeletal muscle; mTOR
资金
- UK Medical Research Council (MRC) [G1100015]
- MRC-Arthritis Research UK (ARUK) Centre for Musculoskeletal Ageing Research [MR/K00414X/1, 19891]
- MRC [G1100015] Funding Source: UKRI
- Medical Research Council [G1100015] Funding Source: researchfish
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-n/1-n/mediated myotube hypertrophy in vitro. Primary skeletal myotubes were treated with IGF-n/1 (50 ng/ml) with or without 0.5 mu MCX-n/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-n/rRNA expression (-64 +/- 5% vs. IGF-n/1; P < 0.001) and total RNA content (-16 +/- 2% vs. IGF-n/1; P < 0.001) in IGF-n/1-n/treated myotubes. IGF-n/1-n/mediated increases in myotube diameter (1.27 +/- 0.09-n/fold, P < 0.05 vs. control) and total protein (+20 +/- 2%; P < 0.001 vs. control) were not prevented by CX treatment. Suppression of rRNAsynthesis during IGF-n/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-n/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-n/1-n/induced myotube hypertrophy in vitro.-n/Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-n/1-n/mediated hypertrophy of human primary myotubes.
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