Cellular Uptake and Bioavailability of Tocotrienol-Rich Fraction in SIRT1-Inhibited Human Diploid Fibroblasts

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.

Analysis of expression of vitamin E-binding proteins in H2O2 induced SK-N-SH neuronal cells supplemented with α-tocopherol and tocotrienol-rich fraction

“…Thus, the bioavailability of vitamin E in the nervous system allows it to carry out its functions [ 6 ]. The current study also complements the findings of a study on the cellular uptake of vitamin E in cultured liver cells, corroborating that the structures of neither vitamin E nor α-TTP play a role in mediating the distribution of vitamin E either in the form of tocopherol or tocotrienol [ 40 ]. It may be mentioned here that other genes related to vitamin E binding (i.e., SEC14L2 , PI-TPNA , and TTPA) are involved in active vitamin E trafficking rather than being only based on passive diffusion, as suggested by Irías-Mata et al [ 26 ].…”

Modulation of Ki67 and myogenic regulatory factor expression by tocotrienol-rich fraction ameliorates myogenic program of senescent human myoblasts

“…Furthermore, as the bioavailability of vitamin E represents its biological activity, the homeostasis of this vitamin in the cell is tightly regulated to prevent toxicity and alteration to the biological system. A previous study showed that the uptake of TRF in senescent cells was higher than in young cells [44]. A similar finding was observed in elderly people, which showed higher uptake of TRF as compared to the young age group [43].…”

Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation

“…TRF naturally exists as a mixture of various forms of vitamin E; all tocotrienol forms are present and highly concentrated in TRF. However, each cell has its own preference for various forms of vitamin E. A previous study showed that the concentration of α- and δ-tocotrienol was the highest in myoblasts, [ 18 ] while γ- and δ-tocotrienol were the most abundant forms in fibroblasts [ 47 ]. As previously described, TRF treatment showed a better effect than single isomer treatment.…”