Estrone sulphate uptake by the microvillous membrane of placental syncytiotrophoblast is coupled to glutamate efflux.
Estrone sulphate uptake by the microvillous membrane of placental syncytiotrophoblast is coupled to glutamate efflux.
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DOI：
10.1016/j.bbrc.2018.10.074
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发表时间：
2018-11-17
影响因子：
3.1
通讯作者：
Lewis RM
中科院分区：
文献类型：
--
作者：
Lofthouse EM;Cleal JK;O'Kelly IM;Sengers BG;Lewis RM
有机阴离子转运蛋白 (OAT) 和有机阴离子转运多肽 (OATP) 是介导代谢物、激素和废物交换的转运蛋白。当交换与其他底物的梯度耦合时，可以发生这些转运蛋白的定向转运。本研究探讨了胎盘合体滋养层母体微绒毛膜上 OATP4A1 和 OATP2A1 的活性是否与谷氨酸梯度相关。 OAT 和 OATP 转运蛋白在非洲爪蟾卵母细胞中过度表达，以研究其转运特性。对足月人胎盘绒毛碎片进行了进一步的转运研究。表达 OATP4A1 介导的谷氨酸摄取的非洲爪蟾卵母细胞。在表达 OAT1、OAT3、OAT7 或 OATP2A1 的卵母细胞中未观察到谷氨酸转运。在表达 OATP4A1 的卵母细胞中，硫酸雌酮、甲状腺激素 T3 和 T4 以及胆汁酸牛磺胆酸盐的摄取刺激谷氨酸流出。在足月胎盘绒毛碎片中添加雌酮硫酸盐和牛磺胆酸盐反式刺激谷氨酸流出。 OATP4A1 与谷氨酸梯度的偶联可能会促进胎盘对硫酸雌酮和甲状腺激素的摄取，同时也促进潜在有害胆汁酸的摄取。相反，如果 OATP2A1 不与类似的梯度偶联，它可能更有效地发挥外排转运蛋白的作用，可能介导前列腺素向母亲的外流。这项研究为谷氨酸作为驱动胎盘转运的重要反离子提供了进一步的证据。 OATP4A1 和 OATP2A1 存在于胎盘母体表面。 OATP4A1（而非 OATP2A1）的活性与谷氨酸流出相关。胎盘雌酮硫酸盐和甲状腺激素的摄取与谷氨酸流出有关。谷氨酸盐充当 OATP4A1 的反离子，驱动转运进入胎盘。
Organic anion transporters (OATs) and organic anion transporting polypeptides (OATPs) are transport proteins that mediate exchange of metabolites, hormones and waste products. Directional transport by these transporters can occur when exchange is coupled to the gradients of other substrates. This study investigates whether the activity of OATP4A1 and OATP2A1 on the maternal facing microvillus membrane of the placental syncytiotrophoblast is coupled to the glutamate gradient. OAT and OATP transporter proteins were over expressed in Xenopus oocytes to study their transport characteristics. Further transport studies were performed in term human placental villous fragments. Xenopus oocytes expressing OATP4A1 mediated glutamate uptake. No glutamate transport was observed in oocytes expressing OAT1, OAT3, OAT7 or OATP2A1. In oocytes expressing OATP4A1, uptake of estrone sulphate, thyroid hormones T3 and T4 and the bile acid taurocholate stimulated glutamate efflux. In term placental villous fragments addition of estrone sulphate and taurocholate trans-stimulated glutamate efflux. Coupling of OATP4A1 to the glutamate gradient may drive placental uptake of estrone-sulphate and thyroid hormone while also facilitating uptake of potentially harmful bile acids. In contrast, if OATP2A1 is not coupled to a similar gradient, it may function more effectively as an efflux transporter, potentially mediating efflux of prostaglandins to the mother. This study provides further evidence for glutamate as an important counter-ion driving transport into the placenta. OATP4A1 and OATP2A1 are present on the maternal facing surface of the placenta. OATP4A1, but not OATP2A1, activity was coupled to glutamate efflux. Placental estrone-sulphate and thyroid hormone uptake is coupled to glutamate efflux. Glutamate acts as a counter-ion for OATP4A1, driving transport into the placenta.
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影响因子：
4.1
作者：
Fork, Christian;Bauer, Tim;Gruendemann, Dirk
通讯作者：
Gruendemann, Dirk
影响因子：
3.7
作者：
Geenes V;Lövgren-Sandblom A;Benthin L;Lawrance D;Chambers J;Gurung V;Thornton J;Chappell L;Khan E;Dixon P;Marschall HU;Williamson C
通讯作者：
Williamson C
谷氨酸循环可能驱动有机阴离子在人胎盘合成细胞基底膜上的转运。
DOI：
10.1113/jp270743
发表时间：
2015-10-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Lofthouse EM;Brooks S;Cleal JK;Hanson MA;Poore KR;O'Kelly IM;Lewis RM
通讯作者：
Lewis RM
DOI：
10.1096/fj.14-267773
发表时间：
2015-06
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Widdows KL;Panitchob N;Crocker IP;Please CP;Hanson MA;Sibley CP;Johnstone ED;Sengers BG;Lewis RM;Glazier JD
通讯作者：
Glazier JD
影响因子：
3.1
作者：
Visser, Theo J.
通讯作者：
Visser, Theo J.