title: Radixin influences the changes in the small intestinal P-glycoprotein by etoposide treatment.
abstract: Previously, we reported that repeated oral administration of etoposide (ETP) increases P-glycoprotein (P-gp) expression in association with activation of ezrin/radixin/moesin (ERM) in the small intestine. Radixin has recently attracted attention for its critical role in the plasma membrane localization of certain drug transporters including P-gp by working as a scaffold protein. However, there have been no report investigating that radixin really interacts with small intestinal P-gp and is involved in the mechanism by which the levels of P-gp are altered. Here, we examined whether radixin is involved in the increased P-gp expression in the small intestine after ETP treatment. Repeated oral treatment with ETP (10 mg/kg/day) for 7 d significantly increased ERM proteins bound to P-gp in the small intestine as determined by immunoprecipitation analysis. In particular, radixin but not ezrin or moesin bound to P-gp was dramatically increased in association with the up-regulation of P-gp in the small intestinal membrane, and radixin was highly co-localized with P-gp as measured by immunofluorescence analysis. In conclusion, radixin may contribute, at least in part, to an increase in the expression of the small intestinal P-gp upon induction with repeated oral treatment with ETP.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University.
authors.forename: Takuro
authors.initials: T
authors.lastname: Kobori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D000099149:Ezrin
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D003598:Cytoskeletal Proteins; D005047:Etoposide; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin