富含生育三烯酚的组分通过靶向胰岛素相关信号通路、DNA损伤、细胞增殖和细胞分化通路中的基因来预防人二倍体成纤维细胞的细胞衰老。

Targeting genes in insulin-associated signalling pathway, DNA damage, cell proliferation and cell differentiation pathways by tocotrienol-rich fraction in preventing cellular senescence of human diploid fibroblasts.

作者信息

Durani L W, Jaafar F, Tan J K, Tajul Arifin K, Mohd Yusof Y A, Wan Ngah W Z, Makpol S

机构信息

Department of Biochemistry, Faculty of Medicine, Level 17, Preclinical Building, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.

出版信息

Clin Ter. 2015 Nov-Dec;166(6):e365-73. doi: 10.7417/T.2015.1902.

DOI:10.7417/T.2015.1902

PMID:26794818

Abstract

BACKGROUND AND OBJECTIVES

Tocotrienols have been known for their antioxidant properties besides their roles in cellular signalling, gene expression, immune response and apoptosis. This study aimed to determine the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs) by targeting the genes in senescence-associated signalling pathways.

MATERIALS AND METHODS

Real time quantitative PCR (qRT-PCR) was utilized to evaluate the expression of genes involved in these pathways.

RESULTS

Our findings showed that SOD1 and CCS-1 were significantly down-regulated in pre-senescent cells while CCS-1 and PRDX6 were up-regulated in senescent cells (p<0.05). Treatment with TRF significantly down-regulated SOD1 in pre-senescent and senescent HDFs, up-regulated SOD2 in senescent cells, CAT in young HDFs, GPX1 in young and pre-senescent HDFs, and CCS-1 in young, pre-senescent and senescent HDFs (p<0.05). TRF treatment also caused up-regulation of FOXO3A in all age groups of cells (p<0.05). The expression of TP53, PAK2 and CDKN2A was significantly increased in senescent HDFs and treatment with TRF significantly down-regulated TP53 in senescent cells (p<0.05). MAPK14 was significantly up-regulated (p<0.05) in senescent HDFs while no changes was observed on the expression of JUN. TRF treatment, however, down-regulated MAPK14 in young and senescent cells and up-regulated JUN in young and pre-senescent HDFs (p<0.05).

CONCLUSIONS

TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.

摘要

背景与目的

生育三烯酚除了在细胞信号传导、基因表达、免疫反应和细胞凋亡中发挥作用外，还以其抗氧化特性而闻名。本研究旨在通过靶向衰老相关信号通路中的基因，确定富含生育三烯酚的组分（TRF）预防人二倍体成纤维细胞（HDFs）细胞衰老的分子机制。

材料与方法

利用实时定量聚合酶链反应（qRT-PCR）评估这些通路中相关基因的表达。

结果

我们的研究结果表明，超氧化物歧化酶1（SOD1）和CCS-1在早衰细胞中显著下调，而CCS-1和过氧化物还原酶6（PRDX6）在衰老细胞中上调（p<0.05）。用TRF处理可显著下调早衰和衰老HDFs中的SOD1，上调衰老细胞中的超氧化物歧化酶2（SOD2）、年轻HDFs中的过氧化氢酶（CAT）、年轻和早衰HDFs中的谷胱甘肽过氧化物酶1（GPX1）以及年轻、早衰和衰老HDFs中的CCS-1（p<0.05）。TRF处理还导致所有年龄组细胞中的叉头框蛋白O3A（FOXO3A）上调（p<0.05）。衰老HDFs中肿瘤蛋白p53（TP53）、p21活化激酶2（PAK2）和细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）的表达显著增加，用TRF处理可显著下调衰老细胞中的TP53（p<0.05）。衰老HDFs中丝裂原活化蛋白激酶14（MAPK14）显著上调（p<0.05），而c-Jun（JUN）的表达未观察到变化。然而，TRF处理可下调年轻和衰老细胞中的MAPK14，并上调年轻和早衰HDFs中的JUN（p<0.05）。