title: Decreased radixin function for ATP-binding cassette transporters in liver in adjuvant-induced arthritis rats.
abstract: Pathophysiological changes are associated with alterations in the expression and function of numerous ADME-related proteins. We have previously demonstrated that the membrane localization of ATP-binding cassette (ABC) transporters in liver was decreased without change of total expression levels in adjuvant-induced arthritis (AA) in rats. Ezrin/radixin/moesin (ERM) proteins are involved in localization of some ABC transporters in canalicular membrane. The mRNA levels of radixin decreased significantly in liver but not kidney, small intestine, and brain. The mRNA levels of ezrin and moesin did not change in AA. The membrane localization of radixin was reduced in liver of AA and the ratios of activated radixin (p-radixin) to total radixin were decreased in AA, although the protein levels of radixin did not change in homogenate and membrane protein. To clarify whether AA affects the linker functions of ERM proteins, we examined the interactions between ERM proteins and ABC transporters. The interactions between radixin and ABC transporters were decreased in AA. In vitro studies using human hepatoma HepG2 cells showed that interleukin-1β decreased the mRNA levels of radixin and colocalization of radixin and Mrp2. Our results show that the decreased radixin functions affect the interaction between radixin and ABC transporters in inflammation.
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kinki University, Osaka 577-8502, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawase
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kinki University, Osaka 577-8502, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Sakata
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kinki University, Osaka 577-8502, Japan.
authors.forename: Nagisa
authors.initials: N
authors.lastname: Yada
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kinki University, Osaka 577-8502, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Nakasaka
authors.affiliation: Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kinki University, Osaka 577-8502, Japan. Electronic address: iwaki@phar.kindai.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwaki
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099149:Ezrin
chemical_list: D018528:ATP-Binding Cassette Transporters; D003598:Cytoskeletal Proteins; D053583:Interleukin-1beta; D008565:Membrane Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D000099149:Ezrin; C071058:moesin; C071776:radixin
keywords: ABC transporters; MRP; P-glycoprotein; active transport; disease states; efflux pumps; elimination; membrane transport; multidrug resistance transporters