Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS) are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in rats, and its possible prevention by allopurinol, a wel...

Total knee arthroplasty (TKA) is the most common and a cost-effective surgical remediation for older adults with long-standing osteoarthritis. In parallel with the expanding population of older adults, the number of TKAs performed annually is projected to be 3.48 million by 2030. During this surgery, a tourniquet is used to stop blood flow to the operative leg. However, the molecular pathways t...

Chronic arthritis induces cachexia associated with an inhibition of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) system and an activation of the E3 ubiquitin-ligating enzymes muscle atrophy F-box (MAFbx) and muscle Ring finger 1 (MuRF1) in the skeletal muscle. The aim of this work was to study the role of cyclooxygenase (COX)-2 in chronic arthritis-induced cachexia. Arthritis wa...

Glucocorticoids (GCs) are important regulators of skeletal muscle mass, and prolonged exposure will induce significant muscle atrophy. To better understand the mechanism of skeletal muscle atrophy induced by elevated GC levels, we examined three different models: exogenous synthetic GC treatment [dexamethasone (DEX)], nutritional deprivation, and denervation. Specifically, we tested the direct ...

TGF-β signalling regulates cell growth, differentiation, morphogenesis and apoptosis. MAFbx/ Atrogin-1 has been identified as a regulator for skeletal muscle atrophy and encodes an F-box-type E3 ubiquitin ligase. However, little is known about how MAFbx/Atrogin-1 regulates cellular signalling. Here, we identify and genetically characterize MFB-1, a MAFbx/Atrogin-1 homologue from Caenorhabditis ...

Tumor necrosis factor receptor-associated factor 6 (TRAF6), a unique E3 ubiquitin ligase and adaptor protein, is involved in activation of various signaling cascades. Recent studies identify TRAF6 as one of the novel regulators of skeletal muscle atrophy. The role of TRAF6 in glucocorticoid-induced muscle atrophy, however, remains to be elucidated. In this study, we show that TRAF6 and its down...

Interleukin-1 (IL-1) is an inflammatory cytokine that has been linked to muscle catabolism, a process regulated by muscle-specific E3 proteins of the ubiquitin-proteasome pathway. To address cellular mechanism, we tested the hypothesis that IL-1 induces myofibrillar protein loss by acting directly on muscle to increase expression of two critical E3 proteins, atrogin1/muscle atrophy F-box (MAFbx...

Proteolytic systems exert an important role in vertebrate muscle controlling protein turnover, recycling of amino acids (AA) or its use for energy production, as well as other functions like myogenesis. In fish, proteolytic systems are crucial for the relatively high muscle somatic index they possess, and because protein is the most important dietary component. Thus in this study, the molecular...

Flywheel-based resistance exercise (RE) attenuates muscle atrophy during hindlimb suspension. We have previously shown that protein synthesis is elevated in response to RE, but the effect on protein degradation, cell proliferation, or apoptosis was not investigated. We hypothesized that, in addition to affecting protein synthesis, RE inhibits processes that actively contribute to muscle atrophy...

BACKGROUND Controlled mechanical ventilation (CMV) is associated with diaphragm dysfunction. Dysfunction results from muscle atrophy and injury of diaphragm muscle fibers. Enhanced proteolysis and reduced protein synthesis play an important role in the development of atrophy. The current study is to evaluate the effects of the calpains inhibitor calpeptin on the development of diaphragm atrophy...