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

Autor: L W, Durani, F, Jaafar, J K, Tan, K, Tajul Arifin, Y A, Mohd Yusof, W Z, Wan Ngah, S, Makpol
Rok vydání: 2016
Předmět:
Zdroj: La Clinica terapeutica. 166(6)
ISSN: 1972-6007
Popis: 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.Real time quantitative PCR (qRT-PCR) was utilized to evaluate the expression of genes involved in these pathways.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 (p0.05). 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 (p0.05). TRF treatment also caused up-regulation of FOXO3A in all age groups of cells (p0.05). The expression of TP53, PAK2 and CDKN2A was significantly increased in senescent HDFs and treatment with TRF significantly down-regulated TP53 in senescent cells (p0.05). MAPK14 was significantly up-regulated (p0.05) 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 (p0.05).TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.
Databáze: OpenAIRE