The Role of Oxidative Stress in Skeletal Muscle Myogenesis and Muscle Disease

Abstract

The contractile activity, high oxygen consumption and metabolic rate of skeletal muscle cause it to continuously produce moderate levels of oxidant species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Under normal physiological conditions, there is a dynamic balance between the production and elimination of ROS/RNS. However, when the oxidation products exceed the antioxidant defense capacity, the body enters a state of oxidative stress. Myogenesis is an important process to maintain muscle homeostasis and the physiological function of skeletal muscle. Accumulating evidence suggests that oxidative stress plays a key role in myogenesis and skeletal muscle physiology and pathology. In this review, we summarize the sources of reactive oxygen species in skeletal muscle and the causes of oxidative stress and analyze the key role of oxidative stress in myogenesis. Then, we discuss the relationship between oxidative stress and muscle homeostasis and physiopathology. This work systematically summarizes the role of oxidative stress in myogenesis and muscle diseases and provides targets for subsequent antioxidant therapy and repair of inflammatory damage in noninflammatory muscle diseases.

Six weeks of N-acetylcysteine antioxidant in drinking water decreases pathological fiber branching in MDX mouse dystrophic fast-twitch skeletal muscle

“…As the mdx mouse model is characterized by a period of florid necrosis 3-20 weeks of age (Duddy et al, 2015) many biochemical changes which are indicative of oxidative damage could be a secondary result of the necrosis, inflammatory response, and subsequent regeneration (Rando, 2002). However, the fact that acute NAC application to the organ bath in in vitro experiments has shown that NAC can prevent eccentric contraction force loss in fast twitch mdx muscles (Whitehead et al, 2008;Olthoff et al, 2018;Lindsay et al, 2020) supports the hypothesis that the absence of dystrophin directly increases the susceptibility the muscle to oxidative triggered damage (Mosca et al, 2021;Lian et al, 2022).…”

“…Here we show NAC treatment reduces the complexity of branched fibers in the fast-twitch mdx EDL muscle, demonstrating that NAC treatment improves mdx fast-twitch muscle pathology. In the dystrophinopahties it has been proposed that the absence of the protein, dystrophin, from the inner surface of the sarcolemma predispose the skeletal muscle to increased oxidative stress and free radical triggered necrosis, which has been identified as a major cause of muscle injury ( Disatnik et al, 2000 ; Mosca et al, 2021 ; Lian et al, 2022 ). The reduction in fiber branching we report here is likely due to NAC reducing ( Rando, 2002 ) the level of free radical triggered necrosis in the active phase of the disease.…”

“…It has been proposed that oxidative stress plays a role in the pathophysiology of Duchenne Muscular Dystrophy (DMD), despite this there is currently no effective antioxidant treatment for DMD ( Mosca et al, 2021 ; Lian et al, 2022 ). N-acetylcysteine (NAC) is an antioxidant that is approved for use in humans, making it attractive as a potential therapeutic treatment for inflammatory conditions in humans ( Mokhtari et al, 2017 ).…”

Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises

“…An excess of FFA is also responsible for deleterious effects on mitochondria such as uncoupling of oxidative phosphorylation, energy failure, decreased clearance, decreased fission, and release of ROSP [ 70 ]. Mitochondrial dysfunction and inflammation/oxidative stress together are responsible for a decrease in myogenesis and muscle function [ 71 ]. In skeletal muscle, elevated ROSP levels concurrently inhibit anabolic pathways as PI3K/Akt/mTOR [ 72 ], contributing to muscle mass loss and atrophy [ 73 , 74 ], and activating several mechanisms of the catabolic pathways ( Figure 1 ).…”

The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H2O2 Exposure

“…ROS levels from low to moderate are critical for cell signaling and regulation of gene expression; they act as signals for cell adaptation and are necessary for muscle growth [ 10 , 12 ]. On the contrary, high levels of ROS with the consequent formation of oxidized macromolecules may contribute to the loss of myoblast function, increase myoblast cell death and worsen muscle repair in aging, events that are associated with metabolic diseases like diabetes or muscle mass loss such as atrophy and sarcopenia [ 13 ]. It is also worth mentioning that many types of physical exercise, especially intense or unaccustomed, result in oxidative stress, as evidenced by increased biomarkers of oxidation in both skeletal muscle and blood [ 12 , 14 , 15 ].…”