IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
artículos
Título:
DISSIMILAR EXPRESION OF MULTIDRUG RESISTANCE MDR1 AND BCRP BY THE REPLICATION OF HEPATITIS C VIRUS: ROLE OF THE NON STRUCTURAL 5A PROTEIN
Autor/es:
RIVERO, CW; ROSSO, N; GENTILE, E; CUESTAS ML; TIRIBELLI, C; OUBIÑA, JR; MATHET, VL
Revista:
JOURNAL OF VIRAL HEPATITIS.
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2013 vol. 24 p. 127 - 130
ISSN:
1352-0504
Resumen:
Multidrug
resistance associated with the 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
nonstructural 5A (NS5A) protein on the expression and functional activity of
two ABC transport proteins: MDR1 and BCRP. RTquantitative real-time polymerase
chain reaction (qPCR) was carried out for mdr1 and bcrp mRNAs in both
Huh7 cells 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.