RRC ID 58125
著者 Kawase A, Nakasaka M, Bando H, Yasuda S, Shimada H, Iwaki M.
タイトル Changes in Radixin Expression and Interaction with Efflux Transporters in the Liver of Adjuvant-Induced Arthritic Rats.
ジャーナル Inflammation
Abstract Scaffold proteins such as radixin help to modulate the plasma membrane localization and transport activity of the multidrug resistance-associated protein 2 (MRP2/ABCC2) and P-glycoprotein (P-gp/ABCB1) efflux transporters in the liver. We examined changes in radixin expression and interaction with efflux transporters in adjuvant-induced arthritic (AA) rats, an animal model of rheumatoid arthritis, as well as in human liver cancer (HepG2) cells because inflammation affects drug pharmacokinetics via the efflux transporters. The expression levels of radixin and phosphorylated radixin (p-radixin) were measured 24 h after treatment with inflammatory cytokines comprising tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 or sodium nitroprusside (SNP; a nitric oxide donor). The protein levels of radixin, MRP2, and P-gp in the rat liver were next examined. We also investigated whether inflammation affected the formation of complexes between radixin and MRP2 or P-gp. The mRNA and protein levels of radixin in HepG2 cells were significantly decreased by TNF-α treatment, while minimal changes were observed after treatment with IL-1β, IL-6 or SNP. TNF-α also significantly decreased the protein levels of p-radixin, suggesting that TNF-α inhibited the activation of radixin and thereby reduced the activity of the efflux transporters. Complex formation of radixin with MRP2 and P-gp was significantly decreased in AA rats but this was reversed by prednisolone and dexamethasone treatment, indicating that decreased interactions of radixin with MRP2 and P-gp likely occur during liver inflammation. These data suggest that liver inflammation reduces radixin function by decreasing its interactions with MRP2 and P-gp.
巻・号 43(1)
ページ 85-94
公開日 2020-2-1
DOI 10.1007/s10753-019-01097-9
PII 10.1007/s10753-019-01097-9
PMID 31654296
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* ATP-Binding Cassette Transporters / metabolism* Animals Anti-Inflammatory Agents / pharmacology Arthritis, Experimental / genetics Arthritis, Experimental / metabolism* Arthritis, Experimental / microbiology Cytokines / pharmacology Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* Female Hep G2 Cells Humans Liver / drug effects Liver / metabolism* Membrane Proteins / genetics Membrane Proteins / metabolism* Multidrug Resistance-Associated Protein 2 Mycobacterium Nitric Oxide Donors / pharmacology Phosphorylation Protein Binding Rats, Sprague-Dawley
IF 3.212
引用数 0
リソース情報
ヒト・動物細胞 Hep G2