Mechanisms of stress-related muscle atrophy in fish: An ex vivo approach

Abstract Muscle development involves coordinated molecular events leading to cell proliferation, fusion, differentiation, sarcomere assembly, and myofibrogenesis. However, under physiological or pathological stress, energy requirements and secretion of glucocorticoids increase, resulting in muscle atrophy because of the depletion of energy reserves. Glucocorticoids induce muscular atrophy by two main mechanisms, protein degradation through the ubiquitin-proteasome system, and inhibition of protein synthesis through the negative regulation of the IGF1-Akt-mTOR signaling pathway. Other signaling pathways (such as the myostatin-activin-smad pathway) involved in muscle atrophy by glucocorticoid exposure are unclear. In fish, the role of glucocorticoids in muscle atrophy has not been fully elucidated. The aim of the present study was to evaluate the mechanisms of muscle atrophy induced by a synthetic glucocorticoid (dexamethasone, DEX) in an ex vivo muscle culture system of a marine fish ( Lutjanus guttatus ). Results showed that DEX was able to induce the expression of myostatin-1 , and the expression of the transcription factor foxo3b . Myostatin-1 silencing by RNAi produced a decrease in the expression of foxo3b and murf1 , and increased the expression of mtor , myod-2 and myogenin . These results suggest that in fish skeletal muscle, myostatin-1 signaling participates in glucocorticoid-induced muscle wasting through the negative regulation of genes involved in muscle growth, such as mtor , myod-2 and myogenin , and the induction of atrophy genes like foxo3b and murf1 .