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经 NPC1 样 1 转运有助于泛醌的肠道吸收。

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

机构信息

Graduate School of Life Science, Hokkaido University, Kita-10-jo, Nishi-8-chome, Kita-ku, Sapporo 060-0810, Japan.

School of Pharmaceutical Sciences and Pharmacy, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.

出版信息

Drug Metab Pharmacokinet. 2020 Dec;35(6):527-533. doi: 10.1016/j.dmpk.2020.08.002. Epub 2020 Aug 18.

Abstract

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.

摘要

泛醌是线粒体电子传递系统的一个组成部分,对于与能量代谢相关的各种活动至关重要,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 蛋白(NPC1L1)参与胆固醇等脂溶性成分的肠道吸收。在本研究中,我们研究了 NPC1L1 是否像胆固醇一样,将泛醌转运到肠道吸收。在本研究中,辅酶 Q10(CoQ10)和辅酶 Q9(CoQ9)被用作泛醌的模型。与 pMAM2-BSD 载体转染的 MDCK 细胞相比,NPC1L1 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 NPC1L1 抑制剂依折麦布存在的情况下,泛醌的摄取减少。这些结果表明 NPC1L1 介导了泛醌的转运。此外,为了阐明 NPC1L1 对 CoQ10 肠道吸收的影响,将乳化 CoQ10 口服给予 Wistar 大鼠,并测量其血浆浓度。与仅给予 CoQ10 相比,依折麦布和 CoQ10 共同给予时 CoQ10 的血浆浓度显著降低。这一结果表明 CoQ10 的肠道吸收是由 NPC1L1 介导的。

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