原创力文档uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations尿毒症毒素抑制多药耐药性乳腺癌抗蛋白质和蛋白质运输4在临床相关的浓度.pdfVIP
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uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations尿毒症毒素抑制多药耐药性乳腺癌抗蛋白质和蛋白质运输4在临床相关的浓度
Uremic Toxins Inhibit Transport by Breast Cancer
Resistance Protein and Multidrug Resistance Protein 4 at
Clinically Relevant Concentrations
1,2 3,5 1 1
Henricus A. M. Mutsaers , Lambertus P. van den Heuvel , Lauke H. J. Ringens , Anita C. A. Dankers ,
1 4 2 1
Frans G. M. Russel , Jack F. M. Wetzels , Joost G. Hoenderop , Rosalinde Masereeuw *
1 Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands,
2 Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands, 3 Department of
Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 4 Department of Nephrology, Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands, 5 Department of Pediatrics, Catholic University Leuven, Leuven, Belgium
Abstract
During chronic kidney disease (CKD), there is a progressive accumulation of toxic solutes due to inadequate renal clearance.
Here, the interaction between uremic toxins and two important efflux pumps, viz. multidrug resistance protein 4 (MRP4) and
breast cancer resistance protein (BCRP) was investigated. Membrane vesicles isolated from MRP4- or BCRP-overexpressing
human embryonic kidney cells were used to study the impact of uremic toxins on substrate specific uptake. Furthermore,
the concentrations of various uremic toxins were determined in plasma of CKD patients using high performance liquid
chromatography and liquid chromatography/tandem mass
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