RRC ID 43837
著者 Sato Y, Suzuki R, Kobayashi M, Itagaki S, Hirano T, Noda T, Mizuno S, Sugawara M, Iseki K.
タイトル Involvement of cholesterol membrane transporter Niemann-Pick C1-like 1 in the intestinal absorption of lutein.
ジャーナル J Pharm Pharm Sci
Abstract PURPOSE: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.
巻・号 15(2)
ページ 256-64
公開日 2012-1-1
DOI 10.18433/j38k56
PMID 22579005
MeSH Adenosine Triphosphatases / antagonists & inhibitors Anticholesteremic Agents / pharmacology Azetidines / pharmacology Caco-2 Cells Cyclopentanes / pharmacology Enzyme Inhibitors / pharmacology Ezetimibe Humans Intestinal Absorption / physiology* Lutein / metabolism* Membrane Proteins / metabolism* Membrane Transport Proteins Scavenger Receptors, Class B / antagonists & inhibitors Scavenger Receptors, Class B / metabolism* Sodium Azide / pharmacology Sodium Fluoride / pharmacology Thiosemicarbazones / pharmacology
IF 1.667
引用数 25
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)