Reference - Detail
| RRC ID | 43329 |
|---|---|
| Author | Narushima K, Takada T, Yamanashi Y, Suzuki H. |
| Title | Niemann-pick C1-like 1 mediates alpha-tocopherol transport. |
| Journal | Mol Pharmacol |
| Abstract |
Dietary lipids and fat-soluble micronutrients are solubilized in mixed micelles and absorbed in the small intestine. Based on an assumption that cholesterol and other fat-soluble molecules share a number of transport mechanisms and the fact that Niemann-Pick C1-like 1 (NPC1L1) is critical for intestinal cholesterol absorption, we hypothesized that some fat-soluble molecules may be transported by NPC1L1. To investigate this hypothesis, we compared the cellular uptake and inhibitory effects of ezetimibe, the molecular target of which is NPC1L1, between cholesterol and some fat-soluble molecules using rat NPC1L1-overexpressing Caco-2 cells. The in vitro analysis suggested that NPC1L1 mediates the uptake of alpha-tocopherol (vitamin E) in an ezetimibe-sensitive manner as well as the uptake of cholesterol but does not mediate the uptake of retinol (vitamin A) or cyclosporin A. To confirm the ezetimibe-sensitive uptake of alpha-tocopherol in vivo, we performed an in vivo absorption study using rats and the results suggested a physiologically significant role of NPC1L1-mediated alpha-tocopherol absorption. Furthermore, using human NPC1L1 overexpression system, we demonstrated that both cholesterol and alpha-tocopherol uptake was also significantly increased by the overexpression of human NPC1L1 and ezetimibe inhibited their uptake. Mutual inhibition studies of cholesterol and alpha-tocopherol in human NPC1L1-mediated uptake revealed the inhibitory effect of cholesterol and the stimulatory effect of alpha-tocopherol on the NPC1L1-mediated transport of both substrates. The present data suggest, for the first time, that NPC1L1 has the ability to transport alpha-tocopherol and that ezetimibe is able to inhibit the intestinal absorption of alpha-tocopherol. |
| Volume | 74(1) |
| Pages | 42-9 |
| Published | 2008-7-1 |
| DOI | 10.1124/mol.107.043034 |
| PII | mol.107.043034 |
| PMID | 18403720 |
| MeSH | Animals Anticholesteremic Agents / pharmacology Azetidines / pharmacology Biological Transport Caco-2 Cells Cholesterol / metabolism Cyclosporine / metabolism Ezetimibe Humans Immunohistochemistry Intestinal Absorption / drug effects Male Membrane Proteins / physiology* Membrane Transport Proteins Micelles Phosphatidylcholines / pharmacology Rats Rats, Wistar Taurocholic Acid / pharmacology Temperature Time Factors Vitamin A / metabolism alpha-Tocopherol / metabolism* |
| IF | 3.664 |
| Times Cited | 97 |
| WOS Category | PHARMACOLOGY & PHARMACY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | |