title: Absorption enhancement effect of acylcarnitines through changes in tight junction protein in Caco-2 cell monolayers.
abstract: We investigated the effects of lauroylcarnitine and palmitoylcarnitine on major tight junction proteins such as claudins in Caco-2 cell monolayers and also examined the involvement of cholesterol in the effects induced by both acylcarnitines on these proteins. We investigated the effects of lauroylcarnitine and palmitoylcarnitine on the barrier function of tight junctions by measuring transepithelial electrical resistance (TEER) and fluorescein isothiocyanate dextran 40,000 (FD-40) flux. A decrease in the TEER value and an increase in FD-40 flux were observed after incubating Caco-2 cell monolayers with lauroylcarnitine and palmitoylcarnitine for 1 h, suggesting the loss of the barrier function of tight junctions. In addition, lauroylcarnitine and palmitoylcarnitine decreased the protein levels of claudin 1, 4, and 5 but not those of claudin 2, 3, 6, or 7. In addition, palmitoylcarnitine and methyl-β-cyclodextrin increased cholesterol release from the plasma membrane. It is suggested that the effects of palmitoylcarnitine and methyl-β-cyclodextrin on claudin 4 and 5 may be associated with cholesterol leakage from the plasma membrane into the apical side. These results indicate that the protein levels of claudin 4 and 5 are decreased by treatment with palmitoylcarnitine and lauroylcarnitine, and that this change is involved in the absorption-enhancing mechanism.
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Doi
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000042:Absorption; D001692:Biological Transport / Q000187:drug effects*; D018938:Caco-2 Cells; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D057167:Claudins / Q000187:drug effects*; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006801:Humans; D007848:Laurates / Q000494:pharmacology*; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D057167:Claudins; D003911:Dextrans; D007848:Laurates; D008565:Membrane Proteins; D047392:beta-Cyclodextrins; C015219:fluorescein isothiocyanate dextran; C108732:methyl-beta-cyclodextrin; D010172:Palmitoylcarnitine; C091947:lauroylcarnitine; D002784:Cholesterol; D016650:Fluorescein-5-isothiocyanate; D002331:Carnitine