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

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.

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

“…They are also transcription factors that assist protein interactions and DNA binding to activate muscle-specific genes [14]. Lim et al found that TRF promoted the proliferation capacity of stress-induced premature senescence myocytes [197]. Moreover, TRF treatment was suggested to modulate the renewal of satellite cells through regulation of p53 signaling, cell cycle, Wnt signaling pathway, and expression of MRF [197].…”

“…Lim et al found that TRF promoted the proliferation capacity of stress-induced premature senescence myocytes [197]. Moreover, TRF treatment was suggested to modulate the renewal of satellite cells through regulation of p53 signaling, cell cycle, Wnt signaling pathway, and expression of MRF [197]. It was also shown to reverse senescence in stress-induced pre-senescence myoblasts, demonstrating the potential therapeutic effects of TRF on senescent muscle cells [198].…”

Multifunctional periodontal membrane for treatment and regeneration purposes

“…Sriram et al 47 induced oxidative stress on adipose derived stem cells with H 2 O 2 and showed that Vit-E treatment decreased ROS levels of oxidative stress induced stem cells and significantly increased adipogenesis compared to untreated control. Lim et al 48 showed that Vit-E treatment increased cell proliferation of human skeletal muscle myoblasts through ErbB and FoxO signaling pathways. Vit-E treatment also regulated the renewal of satellite cells (precursor to skeletal muscle cells).…”

Respiratory muscle senescence in ageing and chronic lung diseases

“…The main trigger for SIPS is oxidative stress. If this stress is experimentally induced in primary myoblast cultures from young subjects, the expression of up to 40 genes becomes modified, predominantly those genes involved in the metabolism of amines, hormonal biosynthesis and activity of lipases [61]. In a relatively recent study carried out on the peripheral muscles of elderly COPD patients with low weight, an increase in proinflammatory factors, oxidative stress and fibrillar damage, as well as regeneration markers, was observed, along with a typical senescent decrease in DNA repair factors, but with no changes in telomere length [62].…”