Leucine alleviates dexamethasone-induced suppression of muscle protein synthesis via synergy involvement of mTOR and AMPK pathways.

Xiao J Wang,Hong C Jiao,Zhi G Song,Xin Yang,Jing P Zhao,Hai Lin,Ru X Wang

doi:10.1042/bsr20160096

Xiao J Wang, Hong C Jiao + Show 5 more

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https://doi.org/10.1042/bsr20160096

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Journal: Bioscience reports	Publication Date: Jun 1, 2016
Citations: 25	License type: CC BY 4.0

Affiliation: Shandong Agricultural University

Abstract

Glucocorticoids (GCs) are negative muscle protein regulators that contribute to the whole-body catabolic state during stress. Mammalian target of rapamycin (mTOR)-signalling pathway, which acts as a central regulator of protein metabolism, can be activated by branched-chain amino acids (BCAA). In the present study, the effect of leucine on the suppression of protein synthesis induced by GCs and the pathway involved were investigated. Invitro experiments were conducted using cultured C2C12 myoblasts to study the effect of GCs on protein synthesis, and the involvement of mTOR pathway was investigated as well. After exposure to dexamethasone (DEX, 100μmol/l) for 24h, protein synthesis in muscle cells was significantly suppressed (P<0.05), the phosphorylations of mTOR, ribosomal protein S6 protein kinase 1 (p70s6k1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) were significantly reduced (P<0.05). Leucine supplementation (5mmol/l, 10mmol/l and 15mmol/l) for 1h alleviated the suppression of protein synthesis induced by DEX (P<0.05) and was accompanied with the increased phosphorylation of mTOR and decreased phosphorylation of AMPK (P<0.05). Branched-chain amino transferase 2 (BCAT2) mRNA level was not influenced by DEX (P>0.05) but was increased by leucine supplementation at a dose of 5mmol/l (P<0.05).

Highlights

The maintenance of skeletal muscle mass is of paramount importance for motility and systemic energy homoeostasis [1]
We demonstrated that the DEX treatment significantly suppressed protein synthesis (P < 0.05, Figure 2A), as well as the phosphorylation of Mammalian target of rapamycin (mTOR), p70s6k1 and 4E binding protein 1 (4EBP1) (P < 0.05, Figures 2B–2D), whereas the total protein
We assessed the direct effect of leucine on muscle protein synthesis in the presence of GCs

Summary

Introduction

The maintenance of skeletal muscle mass is of paramount importance for motility and systemic energy homoeostasis [1]. The control of muscle mass is determined by a dynamic balance between the anabolic and catabolic processes involving proteins [2]. Adrenal glucocorticoids (GCs) are well known to regulate an array of physiological processes, including protein metabolism, contributing to whole-body homoeostasis. Muscle protein synthesis is inhibited as early as 4 h after the administration of GCs [4,5]. Shah et al [6] showed that the injection of dexamethasone (DEX), a synthetic GC, acutely diminished protein synthesis rates to 59 % of control values in skeletal muscle from young rats. The inhibition of mRNA translation initiation appears to be a major mechanism by which GCs result in the inhibition of protein synthesis [7]

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Conclusion