Regulation of the early expression of MAFbx/atrogin-1 and MuRF1 through membrane-initiated cortisol action in the skeletal muscle of rainbow trout
Abstract
Glucocorticoids are key stress-related hormones in vertebrates, with cortisol being the main glucocorticoid in teleosts. Glucocorticoids exert their effects through two mechanisms of action: genomic/classic and membrane initiated. In mammals, cortisol-mediated stress has been found to be associated with increased expression of critical atrophy-related genes (atrogenes), such as MAFbx/atrogin-1 and murf1/trim63. However, the direct impact of cortisol on the early regulation of atrogene expression in teleost skeletal muscle and the contribution of membrane-initiated cortisol action to this process have not been identified. In this work, the mRNA levels of atrogin-1 and murf1 were assessed in isolated myotubes and skeletal muscle of rainbow trout administered with cortisol or cortisol-BSA. This latter compound is a membrane-impermeable cortisol analog that exclusively induces membrane-initiated effects. We found that cortisol (10 mg/kg) first decreased the expression of both atrogenes at 3 h of treatment and then increased their expression at 9 h of treatment in the skeletal muscle of rainbow trout. Additionally, the in vitro analysis suggested that membrane-initiated cortisol action regulates murf1 but not atrogin-1 in rainbow trout myotubes. Using RU486 to selectively block glucocorticoid receptor (GR), we found that early downregulation of murf1 is potentially mediated by membrane GR signaling in myotubes. Considering the results of both the in vivo and in vitro approaches, we suggest that membrane-initiated cortisol action regulates the early expression of atrophy-related processes in teleosts.
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Cortisol induces expression of ubiquitin ligases MuRF1 and Atrogin-1, which tag muscle proteins for degradation via the ubiquitin-proteasome pathway.
“Cortisol induces the expression of ubiquitin ligases like MuRF1 and Atrogin-1, which tag muscle proteins for degradation via the ubiquitin–proteasome pathway.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [82]
Cortisol plays a significant role in muscle proteolysis during caloric restriction.
“Cortisol, a catabolic hormone, plays a significant role in muscle proteolysis during caloric restriction.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [82]
Individuals with high sensitivity to glucocorticoids are more susceptible to muscle loss during caloric restriction.
“Individuals with high sensitivity to glucocorticoids are more susceptible to muscle loss during caloric restriction, as elevated proteolytic activity accelerates muscle catabolism [82].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [82]
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Theodorakis, N., Kreouzi, M., Pappas, A., & Nikolaou, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413438 · Cited by 43 · see citing works
- Authors
- Aravena-Canales, D., Aedo, J. E., Molina, A., & Valdés, J. A.
- Affiliations
- Universidad Andrés Bello (CL)
- Corresponding author
- Valdés, Juan Antonio
- Venue
- Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 253
- Pages
- 110565
- ISSN
- 1096-4959 (ISSN-L)
- OpenAlex
- W3121890724
- Cited by
- 15
- References
- 38
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2
- FWCI
- 0.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (INCAR 15110027)
- Fondo Nacional de Desarrollo Científico y Tecnológico (1171318, 1201498)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- cortisol, atrogin-1, MuRF1, atrogenes, skeletal muscle atrophy, rainbow trout, glucocorticoid receptor, myotubes, stress response, teleosts
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Gene Expression Regulation, Hydrocortisone, Receptors, Glucocorticoid, Oncorhynchus mykiss, Muscle, Skeletal, Fish Proteins
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