pH dependence of methotrexate transport by the reduced folate carrier and the folate receptor in L1210 leukemia cells. Further evidence for a third route mediated at low pH.
pH dependence of methotrexate transport by the reduced folate carrier and the folate receptor in L1210 leukemia cells. Further evidence for a third route mediated at low pH.
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L1210 白血病细胞中减少的叶酸载体和叶酸受体对甲氨蝶呤转运的 pH 依赖性。
DOI：
10.1016/s0006-2952(96)00730-7
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发表时间：
1997
影响因子：
5.8
通讯作者：
Goldman,ID
中科院分区：
文献类型：
--
作者：
Sierra,EE;Brigle,KE;Spinella,MJ;Goldman,ID
F2-MTXrA是一种L1210白血病细胞系，具有还原型叶酸载体的功能缺陷和叶酸受体β的高水平表达。表征了F2-MTXrA细胞中叶酸受体β对甲氨蝶呤（MTX）内流的pH依赖性，并与亲代L1210细胞中还原型叶酸载体的pH依赖性进行了比较。叶酸受体β介导的MTX内流的最适pH值为6.5，而还原叶酸载体介导的内流的最适pH值为7.5。相对于pH 7.5，pH 6.5时叶酸受体β介导的MTX内流增加，伴随着受体对MTX的结合亲和力增加5倍，而结合位点的数量没有变化。在pH 6.2时，F2-MTXrA细胞中约24%的MTX流入通过另一种机制进行。这种转运途径在pH <7.5时变得活跃，在pH 6.0至6.5时最佳，并且与叶酸受体β介导的MTX内流不同，对低水平叶酸（100 nM）的存在不敏感。MTX通过低pH系统的内流显示饱和性，Ki为5.3 μM，Vmax为1.53 nmol/g干重/min，具有能量依赖性，可被磺溴酞抑制，Ki为148 μM，对叶酸、亚叶酸和5-甲基四氢叶酸具有相似的相对亲和力。内流的5-甲基四氢叶酸也介导了这一路线。这些数据为F2-MTXrA细胞中的MTX流入途径提供了进一步的确证性证据，该途径在低pH下最佳，并且与还原叶酸载体或叶酸受体不同。
F2-MTXrA is an L1210 leukemia cell line with a functional defect in the reduced folate carrier and high level expression of folate receptor β. The pH-dependence of methotrexate (MTX) influx by folate receptor β in F2-MTXrA cells was characterized and compared with that of the reduced folate carrier in parental L1210 cells. MTX influx by folate receptor β had a pH optimum of 6.5, whereas influx mediated by the reduced folate carrier showed a pH optimum of 7.5. Increased folate receptor β-mediated MTX influx at pH 6.5 relative to pH 7.5 was accompanied by a 5-fold increase in binding affinity of the receptor for MTX without a change in the number of binding sites. At pH 6.2, approximately 24% of MTX influx in F2-MTXrA cells proceeded by another mechanism. This transport route became active at pH <7.5, operated optimally at pH 6.0 to 6.5, and, unlike folate receptor β-mediated MTX influx, was insensitive to the presence of low levels of folic acid (100 nM). MTX influx by the low pH system showed saturability, with a Kiof 5.3 μM and a Vmaxof 1.53 nmol/g dry wt/min, was energy dependent, was inhibited by sulfobromophthalein with a Kiof 148 μM, and had similar relative affinities for folic acid, leucovorin, and 5-methyltetrahydrofolate. Influx of 5-methyltetrahydrofolate was also mediated by this route. The data provide further confirmatory evidence for an MTX influx route in F2-MTXrA cells, optimal at low pH and distinct from the reduced folate carrier or the folate receptor.
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DOI：
10.1016/s0021-9258(18)91984-8
发表时间：
1968-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Norman;S. Lichtenstein;Vincent;-T.;Oliverio
通讯作者：
Norman;S. Lichtenstein;Vincent;-T.;Oliverio
培养的人近端小管细胞的叶酸转运和结合。
DOI：
10.1152/ajprenal.1992.263.5.f841
发表时间：
1992
期刊：
The American journal of physiology
影响因子：
--
作者：
McMartin,KE;Morshed,KM;Hazen-Martin,DJ;Sens,DA
通讯作者：
Sens,DA
L1210 白血病细胞系的膜蛋白发生变化，其甲氨蝶呤-四氢叶酸辅助因子转运载体存在易位缺陷。
DOI：
--
发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schuetz,JD;Westin,EH;Matherly,LH;Pincus,R;Swerdlow,PS;Goldman,ID
通讯作者：
Goldman,ID
编码与甲氨蝶呤吸收相关的功能的仓鼠 cDNA 克隆的分离。
DOI：
10.1016/s0021-9258(17)37534-8
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
F. Williams;R. Murray;T. Underhill;W. Flintoff
通讯作者：
W. Flintoff
鉴定大阴离子和阴离子缀合物的外排系统作为 L1210 细胞中甲氨蝶呤外排的介质。
影响因子：
5.8
作者：
Saxena,M;Henderson,GB
通讯作者：
Henderson,GB