Molecular regulation of skeletal muscle mass and the contribution of nitric oxide: A review

Abstract

A variety of internal and external factors such as exercise, nutrition, inflammation, and cancer‐associated cachexia affect the regulation of skeletal muscle mass. Because skeletal muscle functions as a crucial regulator of whole body metabolism, rather than just as a motor for locomotion, the enhancement and maintenance of muscle mass and function are required to maintain health and reduce the morbidity and mortality associated with diseases involving muscle wasting. Recent studies in this field have made tremendous progress; therefore, identification of the mechanisms that regulate skeletal muscle mass is necessary for the physical and nutritional management of both athletes and patients with muscle wasting disease. In this review, we present an overall picture of the interactions regulating skeletal muscle mass, particularly focusing on the insulin‐like growth factor‐I (IGF‐I)/insulin‐Akt‐mammalian target of rapamycin (mTOR) pathway, skeletal muscle inactivity, and endurance and resistance exercise. We also discuss the contribution of nitric oxide (NO) to the regulation of skeletal muscle mass based on the current knowledge of the novel role of NO in these processes.

Loss of melusin is a novel, neuronal NO synthase/FoxO3‐independent master switch of unloading‐induced muscle atrophy

“…Muscle disuse or reduced load, such as occurring to antigravity muscles in bedridden patients, represents a major cause of skeletal muscle atrophy. Among the factors responsible for loss of muscle mass and force, a major role has been attributed to the neuronal NO synthase (nNOS) isoform, whose changes in subcellular distribution result in decreased activity of the enzyme at its physiological subsarcolemmal site and increased sustained activity in the myoplasm . A recent study from this laboratory further demonstrated that nNOS redistribution occurs before the appearance of muscle atrophy and shortly after the exposure to disuse/unloading, that is, after a 6 h unloading bout in the rat soleus muscle and a 8 day bed rest in humans, and is required for the nuclear translocation of the “atrogene” transcription factor FoxO3a …”

α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube

“…Nitric oxide has an important role in muscle hypertrophy, especially hypertrophy mediated by resistance exercise [ 45 ], but its overload attenuates protein synthesis, resulting in myotube wasting [ 46 ]. TNFα and IFNγ co-exposure drastically increases NO secretion from C2C12 myotubes via iNOS overexpression induced by the cooperative signaling of STAT3 and NF-κB [ 21 ].…”

Master Regulators of Muscle Atrophy: Role of Costamere Components

“…The contribution of NO, NOS and nitrosative stress to muscle atrophy development is still controversial, despite of the abundant evidence concerning their involvement in muscle atrophy [ 20 , 90 , 105 , 106 ]. A major point of disagreement concerns the actual availability of NO during muscle atrophy development.…”

“…The beneficial pro-trophic effects of NO are largely recognized [ 113 ] acting on pro-trophic signaling [ 106 ]. Exogenous administration of NO-donors or L-arginine was indeed effective in attenuating unloading-induced muscle atrophy [ 107 , 114 ] and the drop of satellite cell proliferation [ 114 ].…”