title: MA026, an anti-hepatitis C virus compound, opens tight junctions of the epithelial cell membrane.
abstract: MA026 is an antiviral natural compound against hepatitis C virus (HCV). It was recently reported that MA026 binds claudin-1 (CLDN1) and inhibits HCV infection. Although CLDN1 is an important component of tight junctions (TJ) in the epithelial cell layer, the effects of MA026 on the TJ barrier function remained to be revealed. Here we report that MA026 irreversibly opens the TJ. MA026 irreversibly increased FD4 permeability and decreased transepithelial electrical resistance (TER) for at least 5 h. Although MA026 increased Ca2+influx in layered MDCKII cells, the Ca2+influx was less than that of capsaicin, a reversible TJ opener. Moreover, MA026 did not induce the dephosphorylation of cofilin and reorganization of F-actin structure. Although the mechanism is left to be disclosed, these results suggest that MA026 is a novel irreversible TJ opener probably by targeting CLDN1.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Yamasaki
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Shimura
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamisuki
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nagumo
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Takeo
authors.identifier: http://orcid.org/0000-0003-2377-7499
authors.initials: T
authors.lastname: Usui
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology*; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D062445:Claudin-1; D047630:Depsipeptides; C000590314:MA026 compound; D002211:Capsaicin; D002118:Calcium