Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals

Abstract

Miyazaki M, Esser KA. Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals. J Appl Physiol 106: 1367-1373, 2009; doi:10.1152/japplphysiol.91355.2008.-Growth and maintenance of skeletal muscle mass is critical for long-term health and quality of life. Skeletal muscle is a highly adaptable tissue with well-known sensitivities to environmental cues such as growth factors, cytokines, nutrients, and mechanical loading. All of these factors act at the level of the cell and signal through pathways that lead to changes in phenotype through multiple mechanisms. In this review, we discuss the animal and cell culture models used and the signaling mechanisms identified in understanding regulation of protein synthesis in response to mechanical loading/resistance exercise. Particular emphasis has been placed on 1) alterations in mechanical loading and regulation of protein synthesis in both in vivo animal studies and in vitro cell culture studies and 2) upstream mediators regulating mammalian target of rapamycin signaling and protein synthesis during skeletal muscle hypertrophy. mechanical stretch; REDD2; overload; IGF-1; amino acids IT IS WIDELY ACCEPTED that repeated bouts of resistance exercise/ high-force contractions produce compensatory growth of skeletal muscle (35,42,47,95). The increase in skeletal muscle mass results from rates of protein synthesis increased more than changes in protein degradation with the net result being an accumulation of protein and increased fiber area (66,96). While the effect of resistance exercise/contraction on muscle mass has long been recognized, the mechanisms underlying the link between high resistance contractions and muscle growth are, to date, not fully understood.One of the important variables contributing to the growth response in skeletal muscle is the application of mechanical loading. For this review we use mechanical loading very generally as the application of force on the muscle or muscle cell. This force on the muscle can occur via active cross-bridge interactions (such as during concentric, isometric, or eccentric contractions) in a gravity-based environment or via external application of force such as passive stretching. The most established animal model for studying skeletal muscle hypertrophy in response to mechanical loading was described by Dr. A. L. Goldberg (38) and was referred to as work-induced muscle growth. This model is now commonly known as the synergist ablation/mechanical overload model and is a surgical model that involves cutting of the tendon and removal of the gastrocnemius muscle, resulting in loading and compensatory growth of the remaining plantar flexors, the plantaris, and soleus muscles. These muscles are involved in maintenance of posture and walking so are loaded by the body weight of the animal. Muscle mass changes are fairly rapid and the growth is robust, ranging from 40 to 200% depending on the muscle and species studied (7,37,38,53,56). Many labs use this model in their research programs to study mole...

High frequency electrical stimulation reveals a p38-mTOR signaling module correlated with force-time integral

“…Repeated bouts of HFC result in muscle hypertrophy and have been linked to growth-related signaling cascades via growth-factor-independent mechanisms (Hornberger and Chien, 2005;Spangenburg et al, 2008). Changes in similar cascades are seen following perturbations of energy metabolism by high-protein feeding, glucose infusion or treatment with the AMP mimetic 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (Miyazaki and Esser, 2009). Thus, a specific gap in our understanding of the response of muscle to HFC is the relative role of mechanical and metabolic signaling in activation of growthrelated signaling cascades.…”

Expression of cationic amino acid transporters, carcass traits, and performance of growing pigs fed low-protein amino acid-supplemented versus high protein diets

“…In the current study, the expression of the IIB isoform of myosin mRNA in LM or SM was not different between pigs fed the F-AA and the PB-AA diets, and was consistent with the lack of differences in loin eye area and protein weight in carcass. Since the protein synthesis process is regulated by the intracellular presence of available AA (Miyazaki and Esser, 2009), these results suggest that the availability of AA for muscle protein synthesis and accretion was not affected by the form (partially free or totally protein-bound) in which Lys, Thr, and Met were supplied. But, since both diets were AA unbalanced, it is not clear why back fat depth was larger in pigs fed the F-AA diet.…”

Effects of a Single Bout of Aerobic Exercise on Skeletal Muscle Protein Turnover in Mice

“…1 Generally, increase in skeletal muscle mass with exercise and nutrition due to protein synthesis is greater than the decrease due to protein degradation, resulting in protein accumulation and increased muscle fibers. 2 However, the catabolic pathway is accelerated during exercise to supply energy and nutrients for continued muscle contraction. It is well known that amino acid levels and glucose oxidation increase during endurance exercise, and an increase in energy consumption may be necessary for the induction of autophagy.…”