Related Experiment Video
Updated: Jun 26, 2026
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
Alcohol-induced decrease in muscle protein synthesis associated with increased binding of mTOR and raptor: Comparable
Charles H Lang1, Anne M Pruznak, Gerald J Nystrom
1Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. clang@psu.edu.
Nutrition & Metabolism
|January 22, 2009
Summary
Acute alcohol intoxication equally impairs muscle protein synthesis in young and mature rats. However, older rats require a higher alcohol dose to achieve similar blood alcohol levels and muscle protein synthesis inhibition.
Area of Science:
- Muscle physiology
- Biochemistry
- Gerontology
Background:
- Acute alcohol (EtOH) intoxication inhibits muscle protein synthesis by suppressing mTOR-dependent translation initiation.
- Previous studies focused on young, rapidly growing rats, potentially overlooking age-related differences in EtOH's effects on muscle growth.
- This study investigates age-dependent variations in muscle protein synthesis response to acute EtOH intoxication.
Purpose of the Study:
- To test the hypothesis that young rats exhibit a greater decrease in muscle protein synthesis than older mature rats following acute EtOH intoxication.
- To compare the sensitivity of muscle protein synthesis to EtOH across different age groups and alcohol doses.
Main Methods:
- Male F344 rats (young: 3 months; mature: 12 months) received intraperitoneal injections of EtOH (75 or 90 mmol/kg) or saline.
- Gastrocnemius muscle protein synthesis and mTOR pathway activity were measured 2.5 hours post-injection using [³H]-labeled phenylalanine and protein phosphorylation analysis.
- Blood alcohol levels (BALs) were determined to correlate EtOH dose with physiological effects.
Main Results:
- Mature rats had lower BALs than young rats at the same EtOH dose (75 mmol/kg), but a higher dose (90 mmol/kg) in mature rats yielded comparable BALs.
- EtOH similarly reduced muscle protein synthesis in young and high-dose mature rats, accompanied by decreased 4E-BP1 phosphorylation and altered eIF4E complex formation.
- EtOH increased mTOR-raptor binding independently of AMPK and TSC, while low-dose EtOH in mature rats showed no change in protein synthesis but reduced rpS6 and eIF4G phosphorylation.
Conclusions:
- Muscle protein synthesis sensitivity to EtOH is similar in young and mature rats, though mature rats require higher doses for equivalent BALs.
- EtOH-induced muscle protein synthesis reduction is linked to decreased mTOR activity, specifically through reduced 4E-BP1 phosphorylation and increased mTOR-raptor complex formation.
- Age does not alter the fundamental sensitivity of muscle protein synthesis to alcohol's inhibitory effects on the mTOR pathway.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:21Overview of Protein Metabolism
Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
01:29Factors Affecting Protein-Drug Binding: Patient-Related Factors
Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...