Blockade of Metallothioneins 1 and 2 Increases Skeletal Muscle Mass and Strength
Open accessAbstract
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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Knockdown as well as genetic ablation of metallothionein 2 promotes muscle growth in mice probably via the AKT-mTOR axis.
“Mechanistically, knocking down as well as genetic ablation of metallothionein 2 promote muscle growth in mice probably via AKT-mTOR axis29.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [29]
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Effects of lactic acid bacteria on protein metabolism of Sunit lamb
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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
- Publisher
- Informa UK Limited
- Published
- 2017-03-01
- Volume
- 37
- Issue
- 5
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC5311239
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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