title: Involvement of cholesterol membrane transporter Niemann-Pick C1-like 1 in the intestinal absorption of lutein.
abstract: OBJECTIVE
  Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. Since humans cannot synthesize lutein de novo, it must be digested as food. The physiological importance of an orally administered compound depends on its interaction with target tissues. It is therefore important to clarify the absorption mechanism in the intestine. Cholesterol membrane transporters Niemann-Pick C1 Like 1 (NPC1L1) and scavenger receptor class B type 1 (SR-B1) are involved in the intestinal absorption of highly lipophilic compounds including cholesterol. Ezetimibe, a selective inhibitor of intestinal NPC1L1, is the widespread lipid-lowering agent. It is important to investigate the possibility of food-drug interactions in order to prevent undesirable and harmful clinical consequences. The aim of this work was to determine whether NPC1L1, SR-B1 and other transporters are involved in absorption of lutein.
  
  
  METHODS
  Caco-2 cells were used for accumulation and permeability study of lutein. Lutein concentration was determined by an HPLC system. The cDNA of transporters was isolated from total RNA of Caco-2 cells, and the expression of these transporters was confirmed by RT-PCR (reverse transcription-polymerase chain reaction).
  
  
  RESULTS
  Ezetimibe inhibited up to 40% of lutein accumulation by Caco-2 cell monolayers. Block lipid transport 1 (BLT-1), a selective chemical inhibitor of SR-B1, also inhibited lutein accumulation by Caco-2 cells. On the other hand, ATP-depletion reagents (sodium fluoride and sodium azide or carbonyl cyanide m-chlorophenylhydrazone) did not influence the accumulation or permeation of lutein significantly.
  
  
  CONCLUSIONS
  The results show that lutein absorption is, at least in part, mediated by influx transporters NPC1L1 and SR-B1 rather than mediated by efflux transporters such as ABC (ATP-binding cassette) transporters.
authors.affiliation: Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Risa
authors.initials: R
authors.lastname: Suzuki
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Noda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mizuno
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001384:Azetidines / Q000494:pharmacology; D018938:Caco-2 Cells; D003517:Cyclopentanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000069438:Ezetimibe; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D014975:Lutein / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019810:Sodium Azide / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000494:pharmacology
chemical_list: C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; D000924:Anticholesteremic Agents; D001384:Azetidines; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D013882:Thiosemicarbazones; D012969:Sodium Fluoride; D019810:Sodium Azide; D000251:Adenosine Triphosphatases; D000069438:Ezetimibe; D014975:Lutein