Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone
Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone
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DOI：
10.1016/j.dmpk.2020.08.002
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发表时间：
2020-12-01
影响因子：
2.1
通讯作者：
Sato, Yuki
中科院分区：
文献类型：
--
作者：
Nashimoto, Shunsuke;Takekawa, Yuto;Sato, Yuki
泛醌是线粒体电子传递系统中的一个组成部分，是能量代谢相关的各种活动所必需的，但泛醌的详细吸收机制尚不清楚。另一方面，尼曼-匹克C1样1（NPC 1 L1）参与脂溶性成分如胆固醇的肠道吸收。在这项研究中，我们研究了泛醌的肠道吸收是否是由NPC 1 L1转运的胆固醇。在这项研究中，辅酶q10（CoQ 10）和辅酶q9（CoQ 9）被用作泛醌的模型。与pMAM 2-BSD载体转染的MDCK细胞相比，NPC 1 L1过表达的Madin-Darby犬肾（MDCK）细胞中泛醌的转运活性显著增加，并且在存在NPC 1 L1抑制剂依折麦布的情况下，泛醌的摄取降低。这些结果表明NPC 1 L1介导泛醌的转运。此外，为了明确NPC 1 L1对CoQ 10的肠吸收的影响，将乳化的CoQ 10口服给药于Wistar大鼠，并测量血浆浓度。与仅给予CoQ 10相比，依折麦布和CoQ 10联合给药可显著降低CoQ 10的血浆浓度。这一结果表明，辅酶Q10的肠道吸收是由NPC 1 L1介导的。(C)2020年日本异生物学研究学会。由爱思唯尔有限公司出版。保留所有权利。
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.