ArticleAmerican journal of physiology. Endocrinology and metabolism2013
The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 108 citations in OpenAlex.
- Musculoskeletal decay and bone-muscle crosstalk during physical disuse: Mechanisms and integrated countermeasures.Experimental physiology · 2026Review
- Alcohol Consumption During Muscle Disuse Causes Differential Signaling Responses in a Muscle-Specific Manner in Mice.International journal of molecular sciences · 2026Article
- Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Therapeutic ultrasound and passive mobilisation improve motor function and reduce inflammation in skeletal muscle of immobilised Wistar rats.Journal of experimental orthopaedics · 2025Article
- A non-syndromic orofacial cleft risk locus links tRNA splicing defects to neural crest cell pathologies.American journal of human genetics · 2025Article
- Cancer Cachexia.Advances in experimental medicine and biology · 2025Review
- Review
- Bioreactor development for skeletal muscle hypertrophy and atrophy by manipulating uniaxial cyclic strain: proof of concept.NPJ microgravity · 2024Article
- The mechanosensitive geneAmerican journal of physiology. Cell physiology · 2024Article
- Loss of 4E-BPs prevents the hindlimb immobilization-induced decrease in protein synthesis in skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Lipid-independent activation of a muscle-specific PKCα splicing variant.American journal of physiology. Heart and circulatory physiology · 2022Article
- mTORC1 regulates high levels of protein synthesis in retinal ganglion cells of adult mice.The Journal of biological chemistry · 2022Article
- Effects of Various Muscle Disuse States and Countermeasures on Muscle Molecular Signaling.International journal of molecular sciences · 2021Review
- Overexpression of ARHGAP30 suppresses growth of cervical cancer cells by downregulating ribosome biogenesis.Cancer science · 2021Article
- Shared and distinct mechanisms of skeletal muscle atrophy: A narrative review.Ageing research reviews · 2021Review
- Soluble RANKL exaggerates hindlimb suspension-induced osteopenia but not muscle protein balance.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- A deep analysis of the proteomic and phosphoproteomic alterations that occur in skeletal muscle after the onset of immobilization.The Journal of physiology · 2021Article
- Increased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription.Molecular biology of the cell · 2021Article
- Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading.Journal of cachexia, sarcopenia and muscle · 2021Article
- Exercise as a therapy for cancer-induced muscle wasting.Sports medicine and health science · 2020Review
3 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.
Funding
Abstract
Limb immobilization, limb suspension, and bed rest cause substantial loss of skeletal muscle mass, a phenomenon termed disuse atrophy. To acquire new knowledge that will assist in the development of therapeutic strategies for minimizing disuse atrophy, the present study was undertaken with the aim of identifying molecular mechanisms that mediate control of protein synthesis and mechanistic target of rapamycin complex 1 (mTORC1) signaling. Male Sprague-Dawley rats were subjected to unilateral hindlimb immobilization for 1, 2, 3, or 7 days or served as nonimmobilized controls. Following an overnight fast, rats received either saline or L-leucine by oral gavage as a nutrient stimulus. Hindlimb skeletal muscles were extracted 30 min postgavage and analyzed for the rate of protein synthesis, mRNA expression, phosphorylation state of key proteins in the mTORC1 signaling pathway, and mTORC1 signaling repressors. In the basal state, mTORC1 signaling and protein synthesis were repressed within 24 h in the soleus of an immobilized compared with a nonimmobilized hindlimb. These responses were accompanied by a concomitant induction in expression of the mTORC1 repressors regulated in development and DNA damage responses (REDD) 1/2. The nutrient stimulus produced an elevation of similar magnitude in mTORC1 signaling in both the immobilized and nonimmobilized muscle. In contrast, phosphorylation of 70-kDa ribosomal protein S6 kinase 1 (p70S6K1) on Thr(229) and Thr(389) in response to the nutrient stimulus was severely blunted. Phosphorylation of Thr(229) by PDK1 is a prerequisite for phosphorylation of Thr(389) by mTORC1, suggesting that signaling through PDK1 is impaired in response to immobilization. In conclusion, the results show an immobilization-induced attenuation of mTORC1 signaling mediated by induction of REDD1/2 and defective p70S6K1 phosphorylation.
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Registered trials
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