Differential sensitivity of plant and yeast MRP (ABCC)‐mediated organic anion transport processes towards sulfonylureas

FEBS Letters

Forestier, Cyrille¹  Eggmann, Thomas³  Frangne, Nathalie³  Klein, Markus² 

[1] CEA Cadarache, Direction des Sciences du Vivant, Département d’Ecophysiologie Végétale et de Microbiologie, Laboratoire des Echanges Membranaires et Signalisation, UMR 163 CNRS-CEA, F-13108 St Paul-lez-Durance, France;Zurich Basel Plant Science Center, Plant Biology, University of Zurich, Zollikerstrasse 107, 8008 Zurich, Switzerland;Université de Neuchâtel, Institut de Botanique, Laboratoire de Physiologie végétale, Rue Emile Argand 13, CH-2007 Neuchâtel, Switzerland

关键词: ATP-binding cassette transporter;    Multidrug resistance-associated protein;    Organic anion transport;    Vacuole transport;    Sulfonylurea;    Fluorescent dye;    ABC;    ATP-binding cassette;    BCECF;    (2′;    7′-bis-(2-carboxyethyl)-5-(and-6-)carboxyfluorescein;    BmCl;    monochlorobimane;    CFTR;    cystic fibrosis transmembrane conductance regulator;    DNB-GS;    2;    4-dinitrobenzene glutathione;    E217G;    β-estradiol 17-(β-D-glucuronide);    GSH;    reduced glutathione;    GSSG;    oxidized glutathione;    GS-X;    glutathione conjugate;    KCO;    potassium channel opener;    LY-CH;    lucifer yellow CH;    MRP;    multidrug resistance-associated protein;    SUR;    sulfonylurea receptor;   

DOI  :  10.1016/S0014-5793(03)01064-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The role of ATP-binding cassette (ABC) proteins such as multidrug resistance-associated proteins (MRPs) is critical in drug resistance in cancer cells and in plant detoxification processes. Due to broad substrate spectra, specific modulators of these proteins are still lacking. Sulfonylureas such as glibenclamide are used to treat non-insulin-dependent diabetes since they bind to the sulfonylurea receptor. Glibenclamide also inhibits the cystic fibrosis transmembrane conductance regulator, p-glycoprotein in animals and guard cell ion channels in plants. To investigate whether this compound is a more general blocker of ABC transporters the sensitivity of ABC-type transport processes across the vacuolar membrane of plants and yeast towards glibenclamide was evaluated. Glibenclamide inhibits the ATP-dependent uptake of β-estradiol 17-(β-D-glucuronide), lucifer yellow CH, and (2′,7′-bis-(2-carboxyethyl)-5-(and-6-)carboxyfluorescein. Transport of glutathione conjugates into plant but not into yeast vacuoles was drastically reduced by glibenclamide. Thus, irrespective of the homologies between plant, yeast and animal MRP transporters, specific features of plant vacuolar MRPs with regard to sensitivity towards sulfonylureas exist. Glibenclamide could be a useful tool to trap anionic fluorescent indicator dyes in the cytosol.

【 授权许可】

Unknown