ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 138 citations in OpenAlex.
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- Hot melt extruded Kyungohkgo attenuates skeletal muscle atrophy by downregulating the FOXO3a/MuRF-1/atrogin-1 axis.Scientific reports · 2026Article
- Fucoidan P Alleviates Sarcopenic Obesity by Regulating Muscle Protein and Energy Metabolism.International journal of biological sciences · 2026Article
- Anti-Atrophic Effects of Dichotomine B fromMolecules (Basel, Switzerland) · 2025Article
- Resistance exercise and skeletal muscle: protein synthesis, degradation, and controversies.European journal of applied physiology · 2025Review
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- Fucosterol, a Phytosterol of Marine Algae, Attenuates Immobilization-Induced Skeletal Muscle Atrophy in C57BL/6J Mice.Marine drugs · 2024Article
- A Mixture ofJournal of microbiology and biotechnology · 2023Article
- FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.Acta pharmacologica Sinica · 2022Article
- Pathogenesis of sarcopenia in chronic obstructive pulmonary disease.Frontiers in physiology · 2022Review
- Fermented Oyster Extract Attenuated Dexamethasone-Induced Muscle Atrophy by Decreasing Oxidative Stress.Molecules (Basel, Switzerland) · 2021Article
- Role of miRNAs and lncRNAs in dexamethasone-induced myotube atrophyExperimental and therapeutic medicine · 2021Article
- Exercise Training-IncreasedFrontiers in aging neuroscience · 2021Article
- Cancer-Associated Muscle Wasting-Candidate Mechanisms and Molecular Pathways.International journal of molecular sciences · 2020Review
- Short-Term Resistance Training Supported by Whole-Body Cryostimulation Induced a Decrease in Myostatin Concentration and an Increase in Isokinetic Muscle Strength.International journal of environmental research and public health · 2020Article
- Iron Status in Elderly Women Impacts Myostatin, Adiponectin and Osteocalcin Levels Induced by Nordic Walking Training.Nutrients · 2020Article
- Protective Effect ofMarine drugs · 2019Article
- Protein synthesis signaling in skeletal muscle is refractory to whey protein ingestion during a severe energy deficit evoked by prolonged exercise and caloric restriction.International journal of obesity (2005) · 2019Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Muscle atrophy is a consequence of chronic diseases (e.g., diabetes) and glucocorticoid-induced insulin resistance that results from enhanced activity of the ubiquitin-proteasome pathway. The PI3K/Akt pathway inhibits the FOXO-mediated transcription of the muscle-specific E3 ligase atrogin-1/MAFbx (AT-1), whereas the MEK/ERK pathway increases Sp1 activity and ubiquitin (UbC) expression. The observations raise a question about how the transcription of these atrogenes is synchronized in atrophic muscle. We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression. In rat L6 myotubes, dexamethasone (> or = 24 h) reduced insulin receptor substrate (IRS)-1 protein and PI3K/Akt signaling and increased AT-1 mRNA. IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, and UbC transcription were simultaneously increased. Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated expression of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression. Changes in PI3K/Akt and MEK/ERK signaling were recapitulated in rat muscles undergoing atrophy due to streptozotocin-induced insulin deficiency and concurrently elevated glucocorticoid production. IRS-1 and Akt phosphorylation were decreased, whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased. We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy.
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