The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin

Abstract

Vitamin E is classified into tocopherol (Toc) and tocotrienol (T3) based on its side chains. T3 generally has higher cellular uptake than Toc, though the responsible mechanism remains unclear. To elucidate this mechanism, we hypothesized and investigated whether serum albumin is a factor that induces such a difference in the cellular uptake of Toc and T3. Adding bovine serum albumin (BSA) to serum-depleted media increased the cellular uptake of T3 and decreased that of Toc, with varying degrees among α-, β-, γ-, and δ-analogs. Such enhanced uptake of α-T3 was not observed when cells were incubated under low temperature (the uptake of α-Toc was also reduced), suggesting that Toc and T3 bind to albumin to form a complex that results in differential cellular uptake of vitamin E. Fluorescence quenching study confirmed that vitamin E certainly bound to BSA, and that T3 showed a higher affinity than Toc. Molecular docking further indicated that the differential binding energy of Toc or T3 to BSA is due to the Van der Waals interactions via their side chain. Overall, these results suggested that the affinity of Toc and T3 to albumin differs due to their side chains, causing the difference in their albumin-mediated cellular uptake. Our results give a better mechanistic insight into the physiological action of vitamin E.

Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment

“…The stability of curcumin can be affected by nanoformulation, e.g., when encapsulated into vesicles of soy lecithin of about 100 nm in diameter, wherein a synergistic effect of concentration and confinement was observed as a result of keto to enol tautomerization [ 14 ]. Furthermore, once in circulation, curcumin may become stabilized by binding to serum albumin that may, similarly to vitamin E, facilitate its transport across the vasculature into tissues and cells [ 7 , 49 , 50 ]. Curcumin is more stable in a cell culture medium containing 10% fetal calf serum as well as in human blood; 50% of curcumin is still intact after 8 h of incubation [ 25 ].…”

α-Tocopherol: New Perspectives and Challenges for Achieving the Sustainable Development Goals (SDG) Target

“…Moreover, the cellular uptake and distribution of Tocs and tocotrienols are different 123) . The Nakagawa group recently demonstrated that Tocs and tocotrienols exhibit varying affinities for albumin, which could potentially lead to differences in their cellular uptake 124) . These reports suggest the significance of the structure and types of binding proteins in determining the intracellular localization of VE.…”