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 th...

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Main Authors: Takashi Nakatomi, Mayuko Itaya-Takahashi, Yosuke Horikoshi, Naoki Shimizu, Isabella Supardi Parida, Mirinthorn Jutanom, Takahiro Eitsuka, Yoshikazu Tanaka, Jean-Marc Zingg, Tatsuya Matsura, Kiyotaka Nakagawa
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-34584-z
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author Takashi Nakatomi
Mayuko Itaya-Takahashi
Yosuke Horikoshi
Naoki Shimizu
Isabella Supardi Parida
Mirinthorn Jutanom
Takahiro Eitsuka
Yoshikazu Tanaka
Jean-Marc Zingg
Tatsuya Matsura
Kiyotaka Nakagawa
author_facet Takashi Nakatomi
Mayuko Itaya-Takahashi
Yosuke Horikoshi
Naoki Shimizu
Isabella Supardi Parida
Mirinthorn Jutanom
Takahiro Eitsuka
Yoshikazu Tanaka
Jean-Marc Zingg
Tatsuya Matsura
Kiyotaka Nakagawa
author_sort Takashi Nakatomi
collection DOAJ
description 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.
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spelling doaj.art-b23db5b6086346a4b49f3c07308cdc562023-05-07T11:10:29ZengNature PortfolioScientific Reports2045-23222023-05-0113111110.1038/s41598-023-34584-zThe difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albuminTakashi Nakatomi0Mayuko Itaya-Takahashi1Yosuke Horikoshi2Naoki Shimizu3Isabella Supardi Parida4Mirinthorn Jutanom5Takahiro Eitsuka6Yoshikazu Tanaka7Jean-Marc Zingg8Tatsuya Matsura9Kiyotaka Nakagawa10Laboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityLaboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityDivision of Medical Biochemistry, Department of Pathophysiological and Therapeutic Sciences, Tottori University Faculty of MedicineLaboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityLaboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityLaboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityLaboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityApplied Biological Molecular Science, Graduate School of Life Sciences, Tohoku UniversityDepartment of Biochemistry and Molecular Biology, University of MiamiDivision of Medical Biochemistry, Department of Pathophysiological and Therapeutic Sciences, Tottori University Faculty of MedicineLaboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku UniversityAbstract 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.https://doi.org/10.1038/s41598-023-34584-z
spellingShingle Takashi Nakatomi
Mayuko Itaya-Takahashi
Yosuke Horikoshi
Naoki Shimizu
Isabella Supardi Parida
Mirinthorn Jutanom
Takahiro Eitsuka
Yoshikazu Tanaka
Jean-Marc Zingg
Tatsuya Matsura
Kiyotaka Nakagawa
The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
Scientific Reports
title The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
title_full The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
title_fullStr The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
title_full_unstemmed The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
title_short The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
title_sort difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
url https://doi.org/10.1038/s41598-023-34584-z
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