Valproic acid transport in the choriocarcinoma placenta cell line JEG-3 proceeds independently of the proton-dependent transporters MCT1 and MCT4
Valproic acid transport in the choriocarcinoma placenta cell line JEG-3 proceeds independently of the proton-dependent transporters MCT1 and MCT4
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DOI：
10.1016/j.dmpk.2018.03.004
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发表时间：
2018-12-01
影响因子：
2.1
通讯作者：
Iseki, Ken
中科院分区：
文献类型：
--
作者：
Ishiguro, Yuri;Furugen, Ayako;Iseki, Ken
药物治疗是治疗癫痫的第一线。胎儿暴露于丙戊酸（VPA），一种抗癫痫药物，会增加妊娠早期致畸性的风险。一些研究报告称，单羧酸转运蛋白（MCT）可能参与VPA的胎盘转运。然而，尚未确定哪些MCT有助于VPA转运至胎盘。因此，本研究的目的是使用人胎盘绒毛膜癌细胞系JEG-3确定MCT如何促进VPA转运至胎盘。使用JEG-3细胞和放射性标记的VPA研究VPA摄取。RT-PCR和Western blotting检测JEG-3细胞中MCT的表达。使用siRNA进行MCT的敲低。JEG-3细胞对VPA的摄取具有pH和浓度依赖性，并使用Michaelis-Menten方程进行描述（Km- 0.95 +/- 0.17 mM; V-max - 19.3 +/- 1.21 nmol/mg蛋白质/15 s）。在JEG-3细胞中发现了MCT 1和MCT 4的表达，并且典型的MCT抑制剂显著抑制JEG-3细胞摄取VPA。然而，MCT 1和MCT 4的敲低并未改变VPA摄取。总之，在JEG-3细胞中，VPA转运由质子依赖性转运蛋白介导，而不是由MCT 1和MCT 4介导。(c)2018年日本异生物学研究学会。由爱思唯尔有限公司出版。保留所有权利。
Medication therapy is the first line of treatment in the management of epilepsy. Fetal exposure to valproic acid (VPA), an antiepileptic drug, poses an elevated risk of teratogenicity in early pregnancy. Some studies have reported that monocarboxylate transporters (MCTs) may be involved in the placental transport of VPA. However, it has not been determined which MCTs contribute to VPA transport into the placenta. Therefore, the aim of this study was to determine how MCTs contribute to VPA transport into the placenta using the human placenta choriocarcinoma cell line JEG-3. VPA uptake was investigated using JEG-3 cells and radiolabeled VPA. MCT expression in JEG-3 cells was detected using RT-PCR and western blotting. Knockdown of MCTs was carried out using siRNAs. VPA uptake into JEG-3 cells was pH-and concentration-dependent, and described by using the Michaelis -Menten equation (K-m - 0.95 +/- 0.17 mM; V-max - 19.3 +/- 1.21 nmol/mg protein/15 s). MCT1 and MCT4 expression was found in JEG-3 cells, and typical MCT inhibitors significantly inhibited VPA uptake into JEG-3 cells. However, knockdown of MCT1 and MCT4 did not alter VPA uptake. In conclusion, VPA transport is mediated by a proton-dependent transporter in JEG-3 cells, but not by MCT1 and MCT4. (c) 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.