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Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12

Victoria C Foletta1, Erin L Brown1, Yoshitake Cho2

  • 1Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Australia.

Biochimica Et Biophysica Acta
|September 7, 2013
PubMed

Insights

The stress-responsive gene N-myc downstream-regulated gene 2 (Ndrg2) is regulated by PGC-1α and ERRα in muscle cells. Ndrg2 influences muscle growth, contraction, and protein synthesis, but not mitochondrial biogenesis.

Area of Science:

  • Muscle physiology and molecular biology
  • Cellular stress response mechanisms
  • Transcriptional regulation in muscle

Background:

  • N-myc downstream-regulated gene 2 (Ndrg2) is a stress-responsive tumor suppressor highly expressed in striated muscle.
  • Ndrg2 expression is modulated by anabolic and catabolic signals in muscle cells, but its regulatory mechanisms and biological roles remain unclear.
  • Understanding Ndrg2 regulation is crucial for comprehending muscle adaptation to physiological stress.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of Ndrg2 expression in muscle cells.
  • To investigate the biological functions of Ndrg2 in differentiated myotubes.
  • To determine the relationship between Ndrg2, PGC-1α, and ERRα in muscle.

Main Methods:

  • Analysis of Ndrg2 as a target of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and estrogen-related receptor alpha (ERRα) transcriptional programs.
  • Gene and protein expression profiling in mouse C2C12 myotubes with altered Ndrg2 levels.
  • Assessment of protein synthesis rates and expression of specific muscle-related genes (e.g., myosin heavy chain isoforms).

Main Results:

  • Ndrg2 is a direct transcriptional target of PGC-1α and ERRα and is induced by endurance exercise.
  • Ndrg2 influences muscle growth, contractile properties, MAPK signaling, ion/vesicle transport, and oxidative phosphorylation.
  • Ndrg2 suppression enhances protein synthesis and fast glycolytic myosin expression, while Ndrg2 overexpression reduces protein synthesis and partially inhibits ERRα-induced protein synthesis.

Conclusions:

  • Ndrg2 is a novel PGC-1α/ERRα transcriptional target in C2C12 myotubes.
  • Ndrg2 plays a significant role in regulating protein turnover and genes associated with muscle contraction and function.
  • Ndrg2's influence on muscle adaptation does not extend to PGC-1α/ERRα-regulated mitochondrial biogenesis genes.
Keywords:
BioinformaticsC2C12 myotubeEstrogen-related receptor alpha (ERRα)N-myc downstream-regulated gene 2 (Ndrg2)Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α)Protein synthesis

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