Expression of multidrug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor.
Pharm Res
; 18(5): 565-72, 2001 May.
Article
em En
| MEDLINE
| ID: mdl-11465409
ABSTRACT
PURPOSE:
The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP) in the retinal pigment epithelial (RPE) cells and to further assess whether BAPSG, a novel anionic aldose reductase inhibitor, interacts with MRP.METHODS:
Functional and biochemical evidence for MRP was obtained in a human retinal pigment epithelial (ARPE-19) cell line and primary cultures of human retinal pigment epithelial (HRPE) cells. Fluorescein accumulation and efflux in the presence and absence of MRP inhibitors was used to obtain functional evidence for MRP. Western blots and RT-PCR were used to obtain biochemical evidence for MRP1. The influence of MRP inhibitors on BAPSG accumulation and efflux in ARPE-19 cells was determined to understand its interaction with MRP.RESULTS:
MRP inhibitors increased fluorescein accumulation and reduced efflux in RPE cells. Both cell types exhibited a 190-kDa western blot band corresponding to MRP1 protein and a 287 bp RT-PCR band corresponding to MRP1 mRNA. MRP inhibitors reduced BAPSG efflux and increased its accumulation in ARPE-19 cells.CONCLUSIONS:
MRP is functionally and biochemically active in human RPE cells. Anionic BAPSG is a likely substrate for MRP.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epitélio Pigmentado Ocular
/
Sulfonas
/
Aldeído Redutase
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Inibidores Enzimáticos
/
Glicina
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA