Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters

被引:296
作者
Leslie, EM
Deeley, RG
Cole, SPC [1 ]
机构
[1] Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada
[2] Queens Univ, Canc Res Labs, Kingston, ON K7L 3N6, Canada
基金
加拿大健康研究院; 英国医学研究理事会;
关键词
multidrug resistance protein; ATP-binding cassette transporter; xenobiotic transport; xenotoxin elimination; carcinogen metabolism;
D O I
10.1016/S0300-483X(01)00454-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The 190 kDa multidrug resistance protein 1 (MRP1/ABCCl) is a founding member of a subfamily of the ATP binding cassette (ABC) superfamily of transport proteins and was originally identified on the basis of its elevated expression in multidrug resistant lung cancer cells. In addition to its ability to confer resistance in tumour cells, MRP1 is ubiquitously expressed in normal tissues and is a primary active transporter of GSH, glucuronate and sulfate conjugated and unconjugated organic anions of toxicological relevance. Substrates include lipid peroxidation products, herbicides, tobacco specific nitrosamines, mycotoxins, heavy metals, and natural product and antifolate anti-cancer agents. MRP1 also transports unmodified xenobiotics but often requires GSH to do so. Active efflux is generally an important aspect of cellular detoxification since it prevents the accumulation of conjugated and unconjugated compounds that have the potential to be directly toxic. The related transporters MRP2 and MRP3 have overlapping substrate specificities with MRP1 but different tissue distributions, and evidence that they also have chemoprotective functions are discussed. Finally, MRP homologues have been described in other species including yeast and nematodes. Those isolated from the vascular plant Arabidopsis thaliana (AtMRPs) decrease the cytoplasmic concentration of conjugated toxins through sequestration in vacuoles and are implicated in providing herbicide resistance to plants. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:3 / 23
页数:21
相关论文
共 151 条
  • [1] Allen JD, 2000, CANCER RES, V60, P5761
  • [2] Membrane topology and glycosylation of the human multidrug resistance-associated protein
    Bakos, E
    Hegedus, T
    Hollo, Z
    Welker, E
    Tusnady, GE
    Zaman, GJR
    Flens, MJ
    Varadi, A
    Sarkadi, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) : 12322 - 12326
  • [3] Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions
    Bakos, É
    Evers, R
    Sinkó, E
    Váradi, A
    Borst, P
    Sarkadi, B
    [J]. MOLECULAR PHARMACOLOGY, 2000, 57 (04) : 760 - 768
  • [4] Multidrug resistance protein-mediated transport of chlorambucil and melphalan conjugated to glutathione
    Barnouin, K
    Leier, I
    Jedlitschky, G
    Pourtier-Manzanedo, A
    König, J
    Lehmann, WD
    Keppler, D
    [J]. BRITISH JOURNAL OF CANCER, 1998, 77 (02) : 201 - 209
  • [5] Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins
    Belinsky, MG
    Bain, LJ
    Balsara, BB
    Testa, JR
    Kruh, GD
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (22) : 1735 - 1741
  • [6] Characterization of the enzymatic and nonenzymatic reaction of 13-oxooctadecadienoic acid with glutathione
    Blackburn, ML
    Ketterer, B
    Meyer, DJ
    Juett, AM
    Bull, AW
    [J]. CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (12) : 1364 - 1371
  • [7] Specific protein targets of 13-oxooctadecadienoic acid (13-OXO) and export of the 13-OXO-glutathione conjugate in HT-29 cells
    Blackburn, ML
    Podgorski, I
    Bull, AW
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1999, 1440 (2-3): : 225 - 234
  • [8] A family of drug transporters: The multidrug resistance-associated proteins
    Borst, P
    Evers, R
    Kool, M
    Wijnholds, J
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (16): : 1295 - 1302
  • [9] The multidrug resistance protein family
    Borst, P
    Evers, R
    Kool, M
    Wijnholds, J
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1999, 1461 (02): : 347 - 357
  • [10] Different pattern of MRP localization in ciliated and basal cells from human bronchial epithelium
    Bréchot, JM
    Hurbain, I
    Fajac, A
    Daty, N
    Bernaudin, JF
    [J]. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1998, 46 (04) : 513 - 517