Efflux of sphingoid bases by P-glycoprotein in human intestinal Caco-2 cells

被引：44
作者：
Sugawara, T [1 ]
Kinoshita, M
Ohnishi, M
Tsuzuki, T
Miyazawa, T
Nagata, J
Hirata, T
Saito, M
机构：
[1] Kyoto Univ, Grad Sch Agr, Div Appl Biosci, Kyoto 6068502, Japan
[2] Natl Inst Hlth & Nutr, Inc Adm Agcy, Div Food Sci, Shinjuku Ku, Tokyo 1628636, Japan
[3] Japan Soc Promot Sci, Tokyo 1028471, Japan
[4] Obihiro Univ Agr & Vet Med, Dept Agr & Life Sci, Obihiro, Hokkaido 0808555, Japan
[5] Tohoku Univ, Grad Sch Agr Sci, Food Biodynam Chem Lab, Sendai, Miyagi 9818555, Japan
来源：
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY | 2004年 / 68卷 / 12期
基金：
日本学术振兴会;
关键词：
Caco-2; cells; murtidrug-resistance (MDR)1; P-glycoprotein; sphingoid base; sphingolipids;
D O I：
10.1271/bbb.68.2541
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The aim of this study was to determine whether sphingoid bases that originated from various dietary sources, such as mammals, plants, and fungi, are substrates for P-glycoprotein in differentiated Caco-2 cells, which are used as a model of intestinal epithelial cells. In Caco-2 cells, the uptake of sphingosine, the most common sphingoid base found in mammals, was significantly higher at physiological temperatures than those of cis/trans-8-sphingenine, trans-4, cisitrans-8-sphingadienine, 9-methyl-trans-4, trans-8-sphingadienine, or sphinganine. Verapamil, a potent P-glycoprotein inhibitor, increased the cellular accumulation of sphingoid bases, except for sphingosine, in a dose-dependent manner. Incubation with 1 mum digoxin for 48 h caused up-regulation of multidrug-resistance (MDR)1 mRNA and decreased the accumulation of sphingoid bases in Caco-2 cells, except for sphingosine. Thus P-glycoprotein probably contributes to the selective absorption of sphingosine from dietary sphingolipids in the digestive tract.
引用
收藏
页码：2541 / 2546
页数：6
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