|
Figure 7
The hypothetical pathogenesis mechanism of muscle atrophy induced by excessive exercise in zebrafish. The upregulated genes are shown in red ovals, and the downregulated genes are shown in green ovals. In response to excessive exercise, the muscle cells may undergo the following events: (1) the inhibition of IGF–PI3K signaling and upregulation of AMPK inhibit the function of the TORC1 complex to suppress protein synthesis and promote autophagy; (2) excessive exercise activates FoxO signaling, which promotes the expression of protein hydrolysis, autophagy, and muscle-atrophy-related gene expression; (3) excessive exercise induces oxidative stress, and the accumulation of misfolded proteins in the endoplasmic reticulum and the activation of p53 signaling lead to proteolysis, autophagy, and apoptosis; (4) overtraining inhibits Wnt signaling and the expression of the MCM complex, which suppresses the proliferation of muscle satellites; and (5) excessive exercise destroys ECM–receptor interaction, focal adhesion, and the gap junction of muscle cells, leading to cytoskeleton damage and inducing apoptosis. (Created with BioRender.com.)