Tocotrienol-Rich Fraction (TRF) Treatment Promotes Proliferation Capacity of Stress-Induced Premature Senescence Myoblasts and Modulates the Renewal of Satellite Cells: Microarray Analysis.

Wan Ngah Wan Zurinah,Jing Jye Lim,Vincent Mouly,Abdul Karim Norwahidah

doi:10.1155/2019/9141343

Abstract

Human skeletal muscle is a vital organ involved in movement and force generation. It suffers from deterioration in mass, strength, and regenerative capacity in sarcopenia. Skeletal muscle satellite cells are involved in the regeneration process in response to muscle loss. Tocotrienol, an isomer of vitamin E, was reported to have a protective effect on cellular aging. This research is aimed at determining the modulation of tocotrienol-rich fraction (TRF) on the gene expressions of stress-induced premature senescence (SIPS) human skeletal muscle myoblasts (CHQ5B). CHQ5B cells were divided into three groups, i.e., untreated young control, SIPS control (treated with 1 mM hydrogen peroxide), and TRF-posttreated groups (24 hours of 50 μg/mL TRF treatment after SIPS induction). The differential gene expressions were assessed using microarray, GSEA, and KEGG pathway analysis. Results showed that TRF treatment significantly regulated the gene expressions, i.e., p53 (RRM2B, SESN1), ErbB (EREG, SHC1, and SHC3), and FoxO (MSTN, SMAD3) signalling pathways in the SIPS myoblasts compared to the SIPS control group (p < 0.05). TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of EREG, SHC1, and SHC3) and FoxO (downregulation of expression of MSTN and SMAD3) and maintaining the renewal of satellite cells through p53 signalling (upregulation of RRM2B and SESN1), MRF, cell cycle, and Wnt signalling pathways.

Highlights

Skeletal muscle is one of the largest organs in the body and contributed to 45-55% of the total body weight [1]
Principal component analysis (PCA) is a multivariate statistic which allows viewing of separation between groups of replicates
Most of the studies focused on the effect of tocopherol on the skeletal muscles, but less in vitro findings were reported on the effects of tocotrienol towards human skeletal muscle cells and the mechanism involved remains unclear

Summary

Introduction

Skeletal muscle is one of the largest organs in the body and contributed to 45-55% of the total body weight [1]. Regeneration of skeletal muscle cells deteriorated with the aging process. This muscle degeneration process due to aging is termed sarcopenia [3]. Muscle degeneration started with 0.5–1% after 30 years of age and the rate increases as age reaches 65 years [4]. The mechanism of this degeneration is still yet to be deciphered clearly, but it can involve oxidative stress [5]. Muscle atrophy is reported to be stimulated by the PI3K/Akt and NF-κB signalling pathways [6]. Braun and Gautel proposed that NF-κB would involve in the regulation of atrogin and regulate the catabolism and anabolism of muscle protein [7]

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