ABCG2 transports sulfated conjugates of steroids and xenobiotics
ABCG2 transports sulfated conjugates of steroids and xenobiotics
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DOI：
10.1074/jbc.m212399200
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发表时间：
2003-06-20
影响因子：
4.8
通讯作者：
Sugiyama, Y
中科院分区：
文献类型：
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作者：
Suzuki, M;Suzuki, H;Sugiyama, Y
细胞挤出硫酸盐缀合物的机制尚不清楚。在本研究中，我们利用转染cdna的小鼠淋巴瘤细胞系（P388细胞）的膜泡研究了人野生型ABCG2是否转运雌酮3-硫酸酯（E1S）。ATP刺激[H-3]E1S进入表达abcg2的膜囊，测定[H-3]E1S的Km值为16.6 muM。abcg2介导的[H-3]E1S的转运被SN-38和许多硫酸盐缀合物有效抑制，但不被葡萄糖醛酸盐和谷胱甘肽缀合物或其他阴离子化合物抑制。其他硫酸盐缀合物如[H-3]脱氢表雄酮硫酸盐（DHEAS）和[S-35]4-甲基菊酮硫酸盐（K-m = 12.9 muM）和[S-35]6-羟基5,7-二甲基-2-甲基氨基-4-（3-吡啶基甲基）苯并噻唑（E3040）硫酸盐（K-m = 26.9 muM）也被ABCG2转运。虽然[H-3]甲氨蝶呤、[H-3]17 β -雌二醇-17 β -d -葡萄糖醛酸盐、[H-3]2,4-二硝基苯- s -谷胱甘肽和[C-14]4-甲基伞草酮葡萄糖醛酸盐被ABCG2转运，但与[H-3]E1S相比，转运的程度要小得多。这表明ABCG2优先转运硫酸盐缀合物，E1S和DHEAS是该转运体的潜在生理底物。
The mechanism for the cellular extrusion of sulfated conjugates is still unknown. In the present study, we investigated whether human wild type ABCG2 transports estrone 3-sulfate (E1S) using membrane vesicles from cDNA-transfected mouse lymphoma cell line (P388 cells). The uptake of [H-3]E1S into ABCG2-expressing membrane vesicles was stimulated by ATP, and the Km value for [H-3]E1S was determined to be 16.6 muM. The ABCG2-mediated transport of [H-3]E1S was potently inhibited by SN-38 and many sulfate conjugates but not by glucuronide and glutathione conjugates or other anionic compounds. Other sulfate conjugates such as [H-3] dehydroepiandrosterone sulfate (DHEAS) and [S-35]4-methylumbelliferone sulfate (K-m = 12.9 muM) and [S-35]6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) sulfate (K-m = 26.9 muM) were also transported by ABCG2. Although [H-3]methotrexate, [H-3]17beta-estradiol-17beta-D-glucuronide, [H-3]2,4-dinitrophenyl-S-glutathione, and [C-14]4-methylumbelliferone glucuronide were transported by ABCG2, this took place to a much lesser extent compared with [H-3]E1S. It was suggested that ABCG2 preferentially transports sulfate conjugates and that E1S and DHEAS are the potential physiological substrates for this transporter.