Abstract
Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated muscle atrophy. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. Methods. Mice were fed either 20% casein diet, 20% soy protein isolate diet, 10% glycinin diet containing 10% casein, or 20% glycinin diet. One week later, the right sciatic nerve was cut. The wet weight, cross sectional area (CSA), IGF-1 signaling, and atrogene expression in hindlimb muscles were examined at 1, 3, 3.5, or 4 days after denervation. Results. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Furthermore, dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Dietary soy glycinin partially suppressed the denervation-mediated expression of atrogenes, such as MAFbx/atrogin-1 and MuRF-1, through the protection of IGF-1 signaling estimated by phosphorylation of Akt-1. Conclusions. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice.
Highlights
Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors, such as insulin-like growth factor (IGF-1) and insulin, and increased proteolysis [1,2,3]
We reported previously that unloading stress resulted in skeletal muscle atrophy through the induction and activation of a ubiquitin ligase Casitas Bcell lymphoma-b (Cbl-b) [4]
These results indicate that the Cbl-b-dependent degradation of insulin receptor substrate-1 (IRS-1) is a critical mediator of increased protein degradation and reduced protein synthesis in unloading-induced muscle atrophy
Summary
Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors, such as insulin-like growth factor (IGF-1) and insulin, and increased proteolysis [1,2,3]. We reported previously that unloading stress resulted in skeletal muscle atrophy through the induction and activation of a ubiquitin ligase Casitas Bcell lymphoma-b (Cbl-b) [4]. We demonstrated that Cbl-b-deficient mice were resistant to unloading-induced atrophy and loss of muscle function [4]. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice
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