Cited by 67Muscle Physiology and DisordersNutrition and Health in AgingMuscle metabolism and nutrition

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

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Summermatter, Serge, Bouzan, Anais, Pierrel, Eliane, Melly, Stefan, Stauffer, Daniela, Gutzwiller, Sabine, Nolin, Erin, Dornelas, Christina +4 more·2017·Molecular and Cellular Biology

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.

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Crossref · 10.1128/mcb.00305-16

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Authors
Summermatter, S., Bouzan, A., Pierrel, E., Melly, S., Stauffer, D., Gutzwiller, S., Nolin, E., Dornelas, C., Fryer, C., Leighton-Davies, J., Glass, D. J., & Fournier, B.
Affiliations
Novartis (Switzerland) (CH)
Venue
Molecular and Cellular Biology
Published
2017-03-01
Volume
37
Issue
5
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2566771799
Cited by
66
References
40
Citations by year
2025: 8 · 2024: 11 · 2023: 9 · 2022: 6 · 2021: 4 · 2020: 12 · 2019: 10 · 2018: 4 · 2017: 2
FWCI
2.77
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • The Novartis Repository (Novartis) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
metallothionein-1, metallothionein-2, skeletal muscle atrophy, muscle hypertrophy, muscle strength, Akt signaling, zinc storage, type IIb muscle fibers, muscle anabolism
MeSH terms
Animals, Body Weight, Glucocorticoids, Humans, Hypertrophy, Metallothionein, Muscular Atrophy, Organ Size, Zinc, Signal Transduction, Biomarkers, Up-Regulation, Muscle, Skeletal, Muscle Fibers, Skeletal, Gene Silencing, Muscle Development, Cell Size, Proto-Oncogene Proteins c-akt, Mice, Rats, Muscle Strength, Sarcopenia, TOR Serine-Threonine Kinases

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