Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone

Nashimoto, Shunsuke; Takekawa, Yuto; Takekuma, Yoh; Sugawara, Mitsuru; Sato, Yuki

Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone

Nashimoto, Shunsuke; Takekawa, Yuto; Takekuma, Yoh et al.

Drug metabolism and pharmacokinetics, 2020, 35(6), 527-533

Permalink : https://hdl.handle.net/2115/83758

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アクセス権	open access
URI	https://hdl.handle.net/2115/83758
タイトル	Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone
著者	Nashimoto, Shunsuke ; Takekawa, Yuto ; Takekuma, Yoh ; Sugawara, Mitsuru ; Sato, Yuki
著者名 Nashimoto, Shunsuke
著者名 Takekawa, Yuto
e-Rad_Researcher 00396293 著者名 Takekuma, Yoh
e-Rad_Researcher 60332467 著者名 Sugawara, Mitsuru
e-Rad_Researcher 00564981 著者名 Sato, Yuki
言語	英語
キーワード	Coenzyme Q10 (PubChem CID: 5281915)
	Coenzyme Q9 (PubChem CID: 5280473)
	Niemann-pick C1 like 1
	Ezetimibe
	Intestinal absorption
	Mixed micelle
発行日	2020-12
出版者	Japanese Society for the Study of Xenobiotics（日本薬物動態学会）JSSX
収録物名	Drug metabolism and pharmacokinetics
巻(号)	35(6)
ページ	527-533
抄録	Ubiquinone, which is a component in the electron-transport systems of mitochondria, is essential for various activities related to energy metabolism, but the detailed absorption mechanism of ubiquinone is not clear. On the other hand, Niemann-Pick C1 Like 1 (NPC1L1) is involved in the intestinal absorption of fat-soluble components such as cholesterol. In this study, we investigated whether the intestinal absorption of ubiquinone was transported by NPC1L1 as is cholesterol. In this study, coenzyme q10 (CoQ10) and coenzyme q9 (CoQ9) were used as models of ubiquinone. The transport activity of ubiquinone was increased significantly in NPC1L1-overexpressed Madin-Darby canine kidney (MDCK) cells compared with that in pMAM2-BSD vector-transfected MDCK cells and the uptake of ubiquinone was decreased in the presence of ezetimibe, an inhibitor of NPC1L1. These results indicate that NPC1L1 mediates the transport of ubiquinone. Furthermore, to clarify the effect of NPC1L1 on the intestinal absorption of CoQ10, emulsified CoQ10 was orally administered to Wistar rats, and the plasma concentration was measured. The plasma concentration of CoQ10 was significantly decreased by coadministration of ezetimibe and CoQ10 compared to that with administration of only CoQ10. This result indicates that the intestinal absorption of CoQ10 is mediated by NPC1L1. (C) 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1347-4367
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.dmpk.2020.08.002