title: Displacement of tight junction proteins from detergent-resistant membrane domains by treatment with sodium caprate.
abstract: We have investigated the effect of sodium salt of capric acid (C10) on major tight junction proteins such as claudin and occludin, and also examined the involvement of lipid rafts with C10-induced alterations on these proteins. We firstly examined the C10 effect on the barrier function of tight junctions by measuring transepithelial electrical resistance (TER) and the flux of FITC dextran 4400 (FD-4). As a result, the increase in the FD-4 flux and decrease in the TER value were observed by incubation with C10 (10 mM) for 30 min, suggesting loss of the barrier function. In addition, C10 incubation produced an increase in solubility to Triton X-100 for claudin 4, 5 and occludin but not for claudin 1, 2, 3. Since it has been reported lipid raft disruption causes an increase in Triton X-100 solubility, it is suggested that effect of C10 on these proteins are involved with lipid rafts. From the lipid raft isolation study, we clarified the distribution of these proteins in lipid rafts. These results strongly indicate the displacement of specific tight junction proteins, claudin 4, 5 and occludin, from lipid raft by the treatment with C10 and involvement of this displacement with the absorption enhancing mechanism of C10.
authors.affiliation: Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Sugibayashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Onuki
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D003652:Decanoic Acids / Q000494:pharmacology*; D003911:Dextrans / Q000378:metabolism; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D062793:Occludin; D017830:Octoxynol / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D019108:Tight Junctions / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D003652:Decanoic Acids; D003911:Dextrans; D008565:Membrane Proteins; D062793:Occludin; D047392:beta-Cyclodextrins; C015219:fluorescein isothiocyanate dextran; C108732:methyl-beta-cyclodextrin; C031071:decanoic acid; D017830:Octoxynol; D016650:Fluorescein-5-isothiocyanate