Pyropia yezoensis Protein Prevents Dexamethasone-Induced Myotube Atrophy in C2C12 Myotubes.

Min-Kyeong Lee,Jeong-Wook Choi,Taek-Jeong Nam,Youn Choi

doi:10.3390/md16120497

Min-Kyeong Lee, Jeong-Wook Choi + Show 2 more

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https://doi.org/10.3390/md16120497

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Journal: Marine drugs	Publication Date: Dec 8, 2018
Citations: 13	License type: CC BY 4.0

Affiliation: Pukyong National University

Abstract

Glucocorticoids (GCs), which are endocrine hormones released under stress conditions, can cause skeletal muscle atrophy. This study investigated whether Pyropia yezoensis crude protein (PYCP) inhibits synthetic GCs dexamethasone (DEX)-induced myotube atrophy associated with proteolytic systems. Mouse skeletal muscle C2C12 myotubes were treated with DEX in the presence or absence of PYCP. DEX exposure (100 μM) for 24 h significantly decreased myotube diameter and myogenin expression, which were all increased by treatment with 20 and 40 μg/mL PYCP. Additionally, PYCP significantly reduced the nuclear expression of the forkhead box transcription factors, FoxO1 and FoxO3a, and ubiquitin-proteasome pathway activation. Further mechanistic research revealed that PYCP inhibited the autophagy-lysosome pathway in DEX-induced C2C12 myotubes. These findings indicate that PYCP prevents DEX-induced myotube atrophy through the regulation of FoxO transcription factors, followed by the inhibition of the ubiquitin-proteasome and autophagy-lysosome pathways. Therefore, we suggest that inhibiting these two proteolytic processes with FoxO transcription factors is a promising strategy for preventing DEX-related myotube atrophy.

Highlights

Skeletal muscle accounts for more than 40% of the body and has important functions in metabolism, energy consumption, physical strength, and physical performance, and skeletal muscle mass is maintained by the relative balance of protein synthesis and degradation [1]
Recent studies have shown that sepsis-induced muscle atrophy is induced by a reduction in function of the cross-bridges between actin and myosin, which is at least partially regulated by the mechanisms involved in GCs-induced skeletal muscle atrophy are not fully understood, some researchers have suggested that the inhibition of protein anabolism or stimulation of protein catabolism is responsible [5,6]
Recent evidence indicates that the administration of DEX increases cathepsin-L and light chain 3 (LC3)-I/II expression in rat skeletal muscles [14,15]. These findings suggest that skeletal muscle atrophy induced by GCs exposure is mediated by the activation of the ubiquitin-proteasome and autophagy-lysosome systems

Summary

Introduction

Skeletal muscle accounts for more than 40% of the body and has important functions in metabolism, energy consumption, physical strength, and physical performance, and skeletal muscle mass is maintained by the relative balance of protein synthesis and degradation [1]. Skeletal muscle atrophy occurs when protein degradation exceeds protein synthesis as a result of long periods of rest, sedentary lifestyle, aging, starvation, and many pathological conditions (e.g., diabetes, cancer, HIV, sepsis, immune disorders, and kidney or heart failure) [2,3]. Many pathological conditions are associated with increased circulating levels of glucocorticoids (GCs), which cause muscle atrophy. Recent studies have shown that sepsis-induced muscle atrophy is induced by a reduction in function of the cross-bridges between actin and myosin, which is at least partially regulated by GCs [4]. Previous studies have shown that GCs-induced skeletal muscle atrophy is mediated by the activation of major cellular proteolytic systems, such as the

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