Blockade of Metallothioneins 1 and 2 Increases Skeletal Muscle Mass and Strength

Mol Cell Biol. 2017 Feb 15;37(5):e00305-16. doi: 10.1128/MCB.00305-16. Print 2017 Mar 1.

Abstract

Metallothioneins are proteins that are involved in intracellular zinc storage and transport. Their expression levels have been reported to be elevated in several settings of skeletal muscle atrophy. We therefore investigated the effect of metallothionein blockade on skeletal muscle anabolism in vitro and in vivo We found that concomitant abrogation of metallothioneins 1 and 2 results in activation of the Akt pathway and increases in myotube size, in type IIb fiber hypertrophy, and ultimately in muscle strength. Importantly, the beneficial effects of metallothionein blockade on muscle mass and function was also observed in the setting of glucocorticoid addition, which is a strong atrophy-inducing stimulus. Given the blockade of atrophy and the preservation of strength in atrophy-inducing settings, these results suggest that blockade of metallothioneins 1 and 2 constitutes a promising approach for the treatment of conditions which result in muscle atrophy.

Keywords: muscle metabolism.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Body Weight
  • Cell Size
  • Gene Silencing
  • Glucocorticoids / adverse effects
  • Humans
  • Hypertrophy
  • Metallothionein / metabolism*
  • Mice
  • Muscle Development
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle Strength / physiology*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Atrophy
  • Organ Size
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Sarcopenia / metabolism
  • Sarcopenia / pathology
  • Sarcopenia / physiopathology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation
  • Zinc / metabolism

Substances

  • Biomarkers
  • Glucocorticoids
  • MT2A protein, human
  • Mt2 protein, mouse
  • metallothionein isoform 1
  • Metallothionein
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Zinc