Desforges M, Mynett K J, Jones R L, Greenwood S L, Westwood M, Sibley C P, Glazier J D
Maternal and Fetal Health Research Group, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK.
J Physiol. 2009 Jan 15;587(1):61-72. doi: 10.1113/jphysiol.2008.161331. Epub 2008 Nov 17.
Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth.
胎盘系统A的活性对于胎儿生长所需中性氨基酸的供应至关重要。有三种系统A异构体：SNAT1、SNAT2和SNAT4，但它们各自对系统A介导的转运的贡献尚不清楚。在此，我们使用免疫组织化学证明所有三种异构体均存在于合体滋养层中，表明它们各自在氨基酸跨胎盘转运中发挥作用。接下来，我们测试了一个假设，即使用一种利用SNAT4转运阳离子氨基酸以及系统A特异性底物甲基氨基异丁酸（MeAIB）的独特特性的方法，来检测SNAT4异构体在来自正常人类胎盘的微绒毛质膜囊泡（MVM）中是否具有功能。数据显示，与足月胎盘相比，妊娠早期胎盘的SNAT4对跨MVM的系统A特异性氨基酸转运的贡献更高（分别约为70%和33%，P < 0.01）。在更接近生理条件下使用完整胎盘绒毛片段进行的进一步实验表明，SNAT4对妊娠早期胎盘系统A活性有贡献，但在足月时贡献最小。与此一致的是，蛋白质印迹法显示，与足月相比，妊娠早期MVM中SNAT4蛋白表达更高（P < 0.05）。本研究提供了SNAT4在人胎盘中活性的首个证据，并证明了SNAT4对系统A介导的转运的贡献在妊娠早期和足月之间降低：我们的数据使我们推测，在妊娠后期，SNAT1和/或SNAT2对于正常胎儿生长所需氨基酸的供应更为重要。
