Functional analysis of CFTR chloride channel activity in cells with elevated MDR1 expression |
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Authors: | Cao Lishuang Owsianik Grzegorz Jaspers Martine Janssens Annelies Cuppens Harry Cassiman Jean-Jacques Nilius Bernd |
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Institution: | Laboratory of Physiology, Catholic University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium. grzegorz.owsianik@med.kuleuven.ac.be |
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Abstract: | 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 up-regulation 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. |
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Keywords: | CFTR MDR1 Cystic fibrosis Multidrug resistance cAMP-activated chloride channel doxorubicin Co-expression Patch-clamp technique |
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