title: Effect of knockdown of ezrin, radixin, and moesin on P-glycoprotein function in HepG2 cells.
abstract: Ezrin, radixin, and moesin (ERM) proteins regulate functional expression of certain transporters, but little is known about their effect on P-glycoprotein (P-gp). Here, we investigated the influence of ERM proteins on the expression and activity of P-gp at the transcriptional, translational, and posttranslational levels, using HepG2 as a model cell line. Knockdown of ezrin with RNA interference decreased the level of P-gp messenger RNA. On the contrary, knockdown of radixin caused a decrease of the P-gp gene product at the cell surface, but not in whole cell lysate. Furthermore, a significant increase in accumulation of rhodamine123, a typical P-gp substrate, was observed in radixin knockdown cells, compared with control cells. Knockdown of moesin did not influence the expression or function of P-gp. These results indicate that ezrin influences the expression of P-gp at the translational level, whereas radixin is involved in membrane localization of P-gp in HepG2 cells.
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kano
authors.forename: Sho
authors.initials: S
authors.lastname: Wada
authors.forename: Kaori
authors.initials: K
authors.lastname: Morimoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Takuo
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020112:Rhodamine 123 / Q000378:metabolism; D000099149:Ezrin
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020112:Rhodamine 123; D000099149:Ezrin; C071058:moesin; C071776:radixin