Comparison of methotrexate polyglutamylation in L1210 leukemia cells when influx is mediated by the reduced folate carrier or the folate receptor. Lack of evidence for influx route-specific effects.
Comparison of methotrexate polyglutamylation in L1210 leukemia cells when influx is mediated by the reduced folate carrier or the folate receptor. Lack of evidence for influx route-specific effects.
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当减少的叶酸载体或叶酸受体介导流入时，L1210 白血病细胞中甲氨蝶呤多谷氨酰化的比较。
DOI：
10.1016/0006-2952(96)00347-4
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发表时间：
1996
影响因子：
5.8
通讯作者：
Goldman,ID
中科院分区：
文献类型：
--
作者：
Spinella,MJ;Brigle,KE;Freemantle,SJ;Sierra,EE;Goldman,ID
We previously described a methotrexate-resistant L1210 cell line (MTXrA) that lacks a functional reduced folate carrier and does not appreciably express the folate receptor. In the present study, we utilized MTXrA cell lines stably transfected with cDNAs encoding either the folate receptor or the reduced folate carrier to investigate the influence of the route of folate influx on the rate and extent of methotrexate polyglutamylation. At an extracellular methotrexate concentration of 0.1 μM, influx in the folate receptor transfectant (MTXrA-TF1) and in the reduced folate carrier transfectant (MTXrA-R1) was equal and methotrexate polyglutamates accumulated at an identical rate, but the onset was delayed until dihydrofolate reductase was saturated with the monoglutamate (~3 hr). The onset of polyglutamate formation was immediate and identical among the lines in cells pretreated with the lipophilic dihydrofolate reductase inhibitor trimetrexate to block methotrexate binding to dihydrofolate reductase. The spectra of individual methotrexate polyglutamates that accumulated were similar, with the tetraglutamate present as the predominant form. A 100-fold higher methotrexate concentration was required to detect methotrexate uptake and polyglutamylation in the transport defective parent MTXrA line, demonstrating that diffusion or an unidentified low affinity route also supports polyglutamylation. Since the folate receptor and the reduced folate carrier achieve nearly identical rates of polyglutamylation despite very different mechanisms of methotrexate delivery, the data suggest that transport-mediated substrate channeling to folylpolyglutamate synthetase is unlikely to play a role in tetrahydrofolate metabolism. This study supports the notion that it is the intracellular concentration of methotrexate achieved within the cell that drives polyglutamylation irrespective of its route of entry.
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影响因子：
11.2
作者：
F. Sirotnak;D. F. O'Leary
通讯作者：
F. Sirotnak;D. F. O'Leary
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
二氢叶酸还原酶升高和甲氨蝶呤转运受损是儿童急性淋巴细胞白血病甲氨蝶呤耐药的因素。
影响因子：
20.3
作者：
Matherly,LH;Taub,JW;Ravindranath,Y;Proefke,SA;Wong,SC;Gimotty,P;Buck,S;Wright,JE;Rosowsky,A
通讯作者：
Rosowsky,A
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
L1210 鼠白血病细胞编码叶酸结合蛋白的两种 cDNA 的表征。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brigle,KE;Westin,EH;Houghton,MT;Goldman,ID
通讯作者：
Goldman,ID