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

Tatsuya Sugawara, Mikio Kinoshita, Masao Ohnishi, Tsuyoshi Tsuzuki, Teruo Miyazawa, Junichi Nagata, Takashi Hirata, Morio Saito

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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 sphingosime, the most common sphingoid base found in mammals, was significantly higher at physiological temperatures than those of cis/trans-8-sphingenine, trans-4, cis/trans-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 μM digoxin for 48 h caused up-regulation of murtidrug-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.

Original languageEnglish
Pages (from-to)2541-2546
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Volume68
Issue number12
DOIs
Publication statusPublished - 2004 Dec 1

Keywords

  • Caco-2 cells
  • Murtidrug-resistance (MDR)1
  • P-glycoprotein
  • Sphingoid base
  • Sphingolipids

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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