Abstract
Tocotrienol-rich fraction (TRF) is palm vitamin E that consists of tocopherol and tocotrienol. TRF is involved in important cellular regulation including delaying cellular senescence. A key regulator of cellular senescence, Sirtuin 1 (SIRT1) is involved in lipid metabolism. Thus, SIRT1 may regulate vitamin E transportation and bioavailability at cellular level. This study aimed to determine the role of SIRT1 on cellular uptake and bioavailability of TRF in human diploid fibroblasts (HDFs). SIRT1 gene in young HDFs was silenced by small interference RNA (siRNA) while SIRT1 activity was inhibited by sirtinol. TRF treatment was given for 24 h before or after SIRT1 inhibition. Cellular concentration of TRF isomers was determined according to the time points of before and after TRF treatment at 0, 24, 48, 72 and 96 h. Our results showed that all tocotrienol isomers were significantly taken up by HDFs after 24 h of TRF treatment and decreased 24 h after TRF treatment was terminated but remained in the cell up to 72 h. The uptake of α-tocopherol, α-tocotrienol and β-tocotrienol was significantly higher in senescent cells as compared to young HDFs indicating higher requirement for vitamin E in senescent cells. Inhibition of SIRT1 gene increased the uptake of all tocotrienol isomers but not α-tocopherol. However, SIRT1 inhibition at protein level decreased tocotrienol concentration. In conclusion, SIRT1 may regulate the cellular uptake and bioavailability of tocotrienol isomers in human diploid fibroblast cells while a similar regulation was not shown for α-tocopherol.
Highlights
Vitamin E is considered as a biologically important molecule that has dual roles of its function
Analysis of vitamin E distribution in lipoprotein showed that α-tocopherol is present in all lipoprotein molecules and triglyceride particle (TRP). α-Tocopherol was mostly found in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)[15]
The presence of α-tocopherol is associated with the expression of LDL receptor which is expressed in most tissues16. α-Tocopherol is mainly found in hepatic tissues, skeletal muscle and adipose tissue
Summary
Vitamin E is considered as a biologically important molecule that has dual roles of its function. Previous studies conducted on vitamin E mostly showed the effect of single isomer, either of tocopherol or tocotrienol. Palm TRF is involved in modulating gene expression of longevity protein, SIRT1. The availability of vitamin E in blood plasma is associated with the binding of vitamin E to lipoprotein molecules[14] These findings showed that α-tocopherol has longer half-life which is 8 hours as compared to tocotrienols which is only 4 hours. This study was conducted to determine the bioavailability of tocotrienol isomer in human skin fibroblast cells. The aim of this study was to determine the role of SIRT1 on cellular uptake and bioavailability of tocotrienol isomer in human skin fibroblast cells
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