ATP-dependent Efflux of 2,4-Dinitrophenyl-S-glutathione
ATP-dependent Efflux of 2,4-Dinitrophenyl-S-glutathione
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2,4-二硝基苯基-S-谷胱甘肽的 ATP 依赖性流出
DOI：
--
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发表时间：
1995
影响因子：
4.8
通讯作者：
G. Henderson
中科院分区：
文献类型：
--
作者：
M. Saxena;G. Henderson
利用L1210细胞2，4-二硝基苯基-S-谷胱甘肽(DNP-SG)自内向外转运到囊泡的方法，鉴定和表征了DNP-SG的ATP依赖性外排途径。对不同浓度的[~3H]DNP-SG的ATP依赖摄取的测量表明，存在两种不同的转运系统。在低底物浓度下，转运主要通过高亲和力体系(Km=0.63μM)进行，而在高底物浓度时，主要通过低亲和力体系(Km=450μM)进行。该高亲和力体系被溴磺化邻苯二甲酸(Ki=0.09μM)和乙丙氨酸(Ki=0.44μM)、白三烯C4(Ki=0.20μM)和牛磺酸胆红素双共轭(Ki=0.10μM)组成的谷胱甘肽结合物所抑制。DNP-SG的低亲和力转运系统对胆红素二月桂酸酯(Ki=1.8μM)、吲哚洛芬(Ki=3.0μM)和联苯乙酸(Ki=5.9μM)具有较高的亲和力。对于甲氨蝶呤和胆酸盐外排缺陷的L1210/C7变异体，得到了不同的结果。后者细胞的囊泡具有与亲本细胞相同的低亲和力转运活性，但缺乏高亲和力途径，已被对DNP-SG具有中等亲和力的系统所取代(Km=4.5μM)。这些结果表明，L1210细胞含有两个DNP-SG的单向外排泵，它们对抑制剂的敏感性有很大差异。高亲和力体系表现出对谷胱甘肽偶联物的结合偏好，但也可以容纳大的阴离子偶联物，而低亲和力体系对大的有机阴离子具有结合偏好。变异细胞的结果支持DNP-SG的高亲和力转运系统在完整的L1210细胞中也介导了甲氨蝶呤和胆酸盐的单向外流的假说。
The transport of 2,4-dinitrophenyl-S-glutathione (DNP-SG) into inside-out vesicles from L1210 cells was employed to identify and characterize ATP-dependent efflux routes for DNP-SG. Measurements of ATP-dependent uptake at varying concentrations of [3H]DNP-SG revealed the presence of two distinct transport systems. Transport at low substrate concentrations occurred predominantly via a high affinity system (Km = 0.63 μM), whereas a low affinity system (Km = 450 μM) predominated at high concentrations of substrate. The high affinity system was characterized by a potent inhibition by the glutathione conjugates of bromosulfophthalein (Ki = 0.09 μM) and ethacrynic acid (Ki = 0.44 μM), leukotriene C4 (Ki = 0.20 μM), and the taurate diconjugate of bilirubin (Ki = 0.10 μM). The low affinity transport system for DNP-SG exhibited a high affinity for bilirubin ditaurate (Ki = 1.8 μM), indoprofen (Ki = 3.0 μM), and biphenylacetic acid (Ki = 5.9 μM). Different results were obtained with an L1210/C7 variant which has a defect in the efflux of methotrexate and cholate. Vesicles from the latter cells contain the same low affinity transport activity as parental cells, but the high affinity route is absent and has been replaced by a system with an intermediate affinity for DNP-SG (Km = 4.5 μM). These results indicate that L1210 cells contain two unidirectional efflux pumps for DNP-SG with substantial differences in inhibitor sensitivity. The high affinity system shows a binding preference for glutathione conjugates but can also accommodate large anionic conjugates, whereas the low affinity system has a binding preference for large organic anions. Results with the variant cells support the hypothesis that the high affinity transport system for DNP-SG also mediates the unidirectional efflux of methotrexate and cholate in intact L1210 cells.
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影响因子：
11.2
作者：
F. Sirotnak;D. M. Moccio;C. Young
通讯作者：
F. Sirotnak;D. M. Moccio;C. Young
影响因子：
11.2
作者：
F. Sirotnak;D. F. O'Leary
通讯作者：
F. Sirotnak;D. F. O'Leary
完整大鼠肝细胞和膜囊泡中还原型谷胱甘肽质膜转运的双向机制。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
García-Ruiz,C;Fernández-Checa,JC;Kaplowitz,N
通讯作者：
Kaplowitz,N
L1210 细胞用于甲氨蝶呤流入和流出的运输路线。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Henderson,GB;Zevely,EM
通讯作者：
Zevely,EM
影响因子：
11.2
作者：
G. Jedlitschky;I. Leier;U. Buchholz;M. Center;D. Keppler
通讯作者：
G. Jedlitschky;I. Leier;U. Buchholz;M. Center;D. Keppler