ArticleJournal of cellular biochemistry2010
Alcohol and PRAS40 knockdown decrease mTOR activity and protein synthesis via AMPK signaling and changes in mTORC1 interaction.
Article in Journal of cellular biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- Alcohol induces p53-mediated apoptosis in neural crest by stimulating an AMPK-mediated suppression of TORC1, S6K, and ribosomal biogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- AMPK, a key molecule regulating aging-related myocardial ischemia-reperfusion injury.Molecular biology reports · 2024Review
- Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice.Neural regeneration research · 2024Article
- Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model.Nutrients · 2023Article
- Alcohol, Resistance Exercise, and mTOR Pathway Signaling: An Evidence-Based Narrative Review.Biomolecules · 2022Review
- Activating transcription factor 4-dependent hsa-miR-663a transcription mediates mTORC1/p70S6K1 signaling underleucine deprivation.Frontiers in nutrition · 2022Article
- Association study between relative expression levels of eight genes and growth rate in Hungarian common carp (Saudi journal of biological sciences · 2022Article
- Article
- Loss of tumor protein 53 protects against alcohol-induced facial malformations in mice and zebrafish.Alcoholism, clinical and experimental research · 2021Article
- Investigating the effects of chronic perinatal alcohol and combined nicotine and alcohol exposure on dopaminergic and non-dopaminergic neurons in the VTA.Scientific reports · 2021Article
- Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain.Pharmacological reviews · 2021Review
- Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats.Experimental and therapeutic medicine · 2020Article
- PRAS40 Phosphorylation Correlates with Insulin-Like Growth Factor-1 Receptor-Induced Resistance to Epidermal Growth Factor Receptor Inhibition in Head and Neck Cancer Cells.Molecular cancer research : MCR · 2020Article
- Mechanisms Underlying Muscle Protein Imbalance Induced by Alcohol.Annual review of nutrition · 2018Article
- Article
- FoxO1-AMPK-ULK1 Regulates Ethanol-Induced Autophagy in Muscle by Enhanced ATG14 Association with the BECN1-PIK3C3 Complex.Alcoholism, clinical and experimental research · 2017Article
- The Genetics of Fetal Alcohol Spectrum Disorders.Alcoholism, clinical and experimental research · 2016Review
- Adamts1 mediates ethanol-induced alterations in collagen and elastin via a FoxO1-sestrin3-AMPK signaling cascade in myocytes.Journal of cellular biochemistry · 2015Article
- Autophagy contributes to regulation of the hypoxia response during submergence in Arabidopsis thaliana.Autophagy · 2015Article
- Moderate alcohol induces stress proteins HSF1 and hsp70 and inhibits proinflammatory cytokines resulting in endotoxin tolerance.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The mTORC1 protein kinase complex consists of mTOR, raptor, mLST8/GbetaL and PRAS40. Previously, we reported that mTOR plays an important role in regulating protein synthesis in response to alcohol (EtOH). However, the mechanisms by which EtOH regulates mTORC1 activity have not been established. Here, we investigated the effect of EtOH on the phosphorylation and interaction of components of mTORC1 in C2C12 myocytes. We also examined the specific role that PRAS40 plays in this process. Incubation of myocytes with EtOH (100 mM, 24 h) increased raptor and PRAS40 phosphorylation. Likewise, there were increased levels of the PRAS40 upstream regulators Akt and IRS-1. EtOH also caused changes in mTORC1 protein-protein interactions. EtOH enhanced the binding of raptor and PRAS40 with mTOR. These alterations occurred in concert with increased binding of 14-3-3 to raptor, while the PRAS40 and 14-3-3 interaction was not affected. The shRNA knockdown (KD) of PRAS40 decreased protein synthesis similarly to EtOH. PRAS40 KD increased raptor phosphorylation and its association with 14-3-3, whereas decreased GbetaL-mTOR binding. The effects of EtOH and PRAS40 KD were mediated by AMPK. Both factors increased in vitro AMPK activity towards the substrate raptor. In addition, KD enhanced the activity of AMPK towards TSC2. Collectively, our results indicate that EtOH stabilizes the association of raptor, PRAS40, and GbetaL with mTOR, while likewise increasing the interaction of raptor with 14-3-3. These data suggest a possible mechanism for the inhibitory effects of EtOH on mTOR kinase activity and protein synthesis in myocytes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.