Functional analysis of CFTR chloride channel activity in cells with elevated MDR1 expression

被引:7
作者
Cao, LS
Owsianik, G
Jaspers, M
Janssens, A
Cuppens, H
Cassiman, JJ
Nilius, B
机构
[1] Catholic Univ Louvain, Physiol Lab, B-3000 Louvain, Belgium
[2] Catholic Univ Louvain, Ctr Human Genet, B-3000 Louvain, Belgium
关键词
CFTR; MDR1; cystic fibrosis; multidrug resistance; cAMP-activated chloride channel; doxorubicin; co-expression; patch-clamp technique;
D O I
10.1016/S0006-291X(03)00581-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Using the patch-clamp method, we investigated a relationship between MDR1 expression and its effects on the CFTR channel function. Incubation of CaCo-2 cells with increasing concentrations of doxorubicin resulted in a reduction of CFTR chloride channel activity in a dose-dependent manner. This reduction was associated with a decrease of CFTR mRNA and simultaneous upregulation of MDR1 mRNA in the presence of doxorubicin. Similar alteration of the CFTR function was observed in CaCo-2 cells transiently overexpressing MDR1. No alterations of the cAMP-dependent chloride currents were observed in COS-1 cells transiently co-expressing CFTR and MDR1 from strong CMV promoters. This indicated that repression of CFTR by MDR1 induction requires the presence of the native CFTR promoter. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:248 / 252
页数:5
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