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Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes.
Biochim Biophys Acta 2013; 1833(12):3112-3123BB

Abstract

The stress-responsive, tumor suppressor N-myc downstream-regulated gene 2 (Ndrg2) is highly expressed in striated muscle. In response to anabolic and catabolic signals, Ndrg2 is suppressed and induced, respectively, in mouse C2C12 myotubes. However, little is known about the mechanisms regulating Ndrg2 expression in muscle, as well as the biological role for Ndrg2 in differentiated myotubes. Here, we show that Ndrg2 is a target of a peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and estrogen-related receptor alpha (ERRα) transcriptional program and is induced in response to endurance exercise, a physiological stress known also to increase PGC-1α/ERRα activity. Analyses of global gene and protein expression profiles in C2C12 myotubes with reduced levels of NDRG2, suggest that NDRG2 affects muscle growth, contractile properties, MAPK signaling, ion and vesicle transport and oxidative phosphorylation. Indeed, suppression of NDRG2 in myotubes increased protein synthesis and the expression of fast glycolytic myosin heavy chain isoforms, while reducing the expression of embryonic myosin Myh3, other contractile-associated genes and the MAPK p90 RSK1. Conversely, enhanced expression of NDRG2 reduced protein synthesis, and furthermore, partially blocked the increased protein synthesis rates elicited by a constitutively active form of ERRα. In contrast, suppressing or increasing levels of NDRG2 did not affect mRNA expression of genes involved in mitochondrial biogenesis that are regulated by PGC-1α or ERRα. This study shows that in C2C12 myotubes Ndrg2 is a novel PGC-1α/ERRα transcriptional target, which influences protein turnover and the regulation of genes involved in muscle contraction and function.

Authors+Show Affiliations

Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Australia. Electronic address: victoria.foletta@deakin.edu.au.Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Australia.Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Australia.Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Australia.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24008097

Citation

Foletta, Victoria C., et al. "Ndrg2 Is a PGC-1α/ERRα Target Gene That Controls Protein Synthesis and Expression of Contractile-type Genes in C2C12 Myotubes." Biochimica Et Biophysica Acta, vol. 1833, no. 12, 2013, pp. 3112-3123.
Foletta VC, Brown EL, Cho Y, et al. Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes. Biochim Biophys Acta. 2013;1833(12):3112-3123.
Foletta, V. C., Brown, E. L., Cho, Y., Snow, R. J., Kralli, A., & Russell, A. P. (2013). Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes. Biochimica Et Biophysica Acta, 1833(12), pp. 3112-3123. doi:10.1016/j.bbamcr.2013.08.011.
Foletta VC, et al. Ndrg2 Is a PGC-1α/ERRα Target Gene That Controls Protein Synthesis and Expression of Contractile-type Genes in C2C12 Myotubes. Biochim Biophys Acta. 2013;1833(12):3112-3123. PubMed PMID: 24008097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes. AU - Foletta,Victoria C, AU - Brown,Erin L, AU - Cho,Yoshitake, AU - Snow,Rod J, AU - Kralli,Anastasia, AU - Russell,Aaron P, Y1 - 2013/09/02/ PY - 2013/02/14/received PY - 2013/06/17/revised PY - 2013/08/09/accepted PY - 2013/9/7/entrez PY - 2013/9/7/pubmed PY - 2014/2/25/medline KW - Bioinformatics KW - C2C12 myotube KW - Estrogen-related receptor alpha (ERRα) KW - N-myc downstream-regulated gene 2 (Ndrg2) KW - Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) KW - Protein synthesis SP - 3112 EP - 3123 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1833 IS - 12 N2 - The stress-responsive, tumor suppressor N-myc downstream-regulated gene 2 (Ndrg2) is highly expressed in striated muscle. In response to anabolic and catabolic signals, Ndrg2 is suppressed and induced, respectively, in mouse C2C12 myotubes. However, little is known about the mechanisms regulating Ndrg2 expression in muscle, as well as the biological role for Ndrg2 in differentiated myotubes. Here, we show that Ndrg2 is a target of a peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and estrogen-related receptor alpha (ERRα) transcriptional program and is induced in response to endurance exercise, a physiological stress known also to increase PGC-1α/ERRα activity. Analyses of global gene and protein expression profiles in C2C12 myotubes with reduced levels of NDRG2, suggest that NDRG2 affects muscle growth, contractile properties, MAPK signaling, ion and vesicle transport and oxidative phosphorylation. Indeed, suppression of NDRG2 in myotubes increased protein synthesis and the expression of fast glycolytic myosin heavy chain isoforms, while reducing the expression of embryonic myosin Myh3, other contractile-associated genes and the MAPK p90 RSK1. Conversely, enhanced expression of NDRG2 reduced protein synthesis, and furthermore, partially blocked the increased protein synthesis rates elicited by a constitutively active form of ERRα. In contrast, suppressing or increasing levels of NDRG2 did not affect mRNA expression of genes involved in mitochondrial biogenesis that are regulated by PGC-1α or ERRα. This study shows that in C2C12 myotubes Ndrg2 is a novel PGC-1α/ERRα transcriptional target, which influences protein turnover and the regulation of genes involved in muscle contraction and function. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/24008097/Ndrg2_is_a_PGC_1α/ERRα_target_gene_that_controls_protein_synthesis_and_expression_of_contractile_type_genes_in_C2C12_myotubes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-4889(13)00309-1 DB - PRIME DP - Unbound Medicine ER -