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 |