Khor S C, Mohd Yusof Y A, Wan Ngah W Z, Makpol S
Department of Biochemistry, Level 17, Pre-Clinical Building, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
Clin Ter. 2015;166(2):e81-90. doi: 10.7417/CT.2015.1825.
Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).
Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.
Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.
Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.
维生素E已被提议作为预防退行性疾病和与年龄相关疾病的营养干预措施。在本研究中，我们旨在通过靶向人类二倍体成纤维细胞（HDFs）中的增殖信号通路，阐明富含生育三烯酚的组分（TRF）延缓细胞衰老的潜在机制。
使用富含生育三烯酚的组分处理原代人类二倍体成纤维细胞不同阶段的细胞衰老，即年轻（第6代）、早衰（第15代）和衰老（第30代）细胞。比较了PI3K/AKT和RAF/MEK/ERK通路下游几个选定靶点在总RNA和蛋白质水平的差异。
在年轻、早衰和衰老的HDFs中观察到不同的转录谱，其中细胞衰老使AKT、FOXO3、CDKN1A和RSK1 mRNA表达水平升高，但使ELK1、FOS和SIRT1 mRNA表达水平降低。用富含生育三烯酚的组分处理后，衰老细胞中AKT、FOXO3、ERK和RSK1 mRNA的基因表达降低，但年轻细胞中未降低。细胞衰老过程中下调的三种mRNA，即ELK1、FOS和SIRT1，在用富含生育三烯酚的组分处理后表达增加。FOXO3和P21Cip1蛋白在衰老细胞中表达上调，但富含生育三烯酚的组分仅降低衰老细胞中P21Cip1蛋白的表达。
富含生育三烯酚的组分具有基因调节特性，可能在细胞衰老过程中促进细胞周期进程。
