IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
artículos
Título:
Dissimilar expression of multidrug resistance mdr1 and bcrp by the replication of hepatitis C virus: role of the non structural 5A protein.?
Autor/es:
RIVERO, C; ; ROSSO, N; ; GENTILE, E; .; CUESTAS, M; ; TIRIBELLI, C; ; OUBIÑA, J ; MATHET, V
Revista:
JOURNAL OF VIRAL HEPATITIS.
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2012
ISSN:
1352-0504
Resumen:
Multidrug resistance associated to overexpression of ATP-dependent binding cassette (ABC) proteins is widely accepted as an important cause of treatment failure in patients with neoplastic or infectious diseases. Some of them play also a pivotal role in detoxification processes. Herein, we investigated the effect of hepatitis C virus (HCV) replication and NS5A protein on the expression and functional activity of two ABC transport proteins: MDR1 and BCRP. RT-quantitative real time polymerase chain reaction (qPCR) was carried out for mdr1 and bcrp mRNAs in both Huh7cells expressing NS5A and Huh7.5 cells containing either full-length- or subgenomic-HCV replicon systems. The functional activity of these pumps was studied by performing a dye efflux assay with DiOC2 and Rhodamine 123. A dose-dependent down-regulation of mdr1 expression was documented in Huh7 cells expressing the NS5A protein, as well as in both replicon systems. In contrast, a significant increase of bcrp expression in both systems was recorded, which were in full agreement with the dye efflux assay results. These results warrant further in vivo studies in HCV patients with cholestasis and/or patients that are refractive to the pharmacotherapy due to the activity of these pumps.