Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
Thérapie des Maladies du Muscle Strié Institut de Myologie, UM76-UPMC Univ. Paris 6/ U974-Inserm/UMR7215-CNRS, G.H. Pitié-Salpétrière-INSERM, UMRS 974, Institut de Myologie, Université Pierre et Marie Curie, Paris, France.
Oxid Med Cell Longev. 2019 Jan 10;2019:9141343. doi: 10.1155/2019/9141343. eCollection 2019.
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 g/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 ( < 0.05). TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of , , and ) and FoxO (downregulation of expression of and ) and maintaining the renewal of satellite cells through p53 signalling (upregulation of and ), MRF, cell cycle, and Wnt signalling pathways.
人类骨骼肌是参与运动和力量产生的重要器官。它在肌肉减少症中会出现质量、力量和再生能力的恶化。骨骼肌卫星细胞参与肌肉丢失后的再生过程。生育三烯酚，维生素 E 的一种异构体，据报道对细胞衰老具有保护作用。这项研究旨在确定富含生育三烯酚的馏分 (TRF) 对应激诱导过早衰老 (SIPS) 人类骨骼肌成肌细胞 (CHQ5B) 的基因表达的调节作用。CHQ5B 细胞分为三组，即未处理的年轻对照组、SIPS 对照组（用 1mM 过氧化氢处理）和 TRF 后处理组（SIPS 诱导后 24 小时用 50μg/mL TRF 处理）。使用微阵列、GSEA 和 KEGG 途径分析评估差异基因表达。结果表明，与 SIPS 对照组相比，TRF 处理显著调节了 SIPS 成肌细胞中的基因表达，即 p53（RRM2B、 SESN1）、ErbB（EREG、SHC1 和 SHC3）和 FoxO（MSTN、SMAD3）信号通路（<0.05）。TRF 处理通过调节 ErbB（上调表达 、 和 ）和 FoxO（下调表达 和 ）调节 SIPS 成肌细胞的增殖能力，并通过 p53 信号通路（上调表达 和 ）、MRF、细胞周期和 Wnt 信号通路维持卫星细胞的更新。
