Differential levels of amino acid transporters System L and ASCT2, and the mTOR protein in placenta of preeclampsia and IUGR.
Differential levels of amino acid transporters System L and ASCT2, and the mTOR protein in placenta of preeclampsia and IUGR.
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DOI：
10.1186/1471-2393-14-181
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发表时间：
2014-05-30
影响因子：
3.1
通讯作者：
Shibata E
中科院分区：
文献类型：
--
作者：
Aiko Y;Askew DJ;Aramaki S;Myoga M;Tomonaga C;Hachisuga T;Suga R;Kawamoto T;Tsuji M;Shibata E
充足的氨基酸转运活性（AAT）是胎儿正常生长所必需的。研究表明，胎盘的营养摄取活动是响应母亲和胎儿的营养需求。我们假设，在胎儿营养有限的条件下，如经常出现在先兆子痫，宫内生长受限（IUGR），以及妊娠期间体重增加不足，胎盘中可能会观察到旨在增加氨基酸转运活性的一般适应性反应。通过免疫组织化学观察来自足月（n = 10）和早产（平均妊娠期= 34.8周，n = 10）正常妊娠、IUGR（n = 10）和先兆子痫（n = 10）相关妊娠的总共40个胎盘，随后进行相对定性评分以比较System L、ASCT2和mTOR蛋白的表达水平和定位。合并IUGR或先兆子痫（PE）的胎盘微绒毛合体滋养细胞（ST）中L系统氨基酸转运蛋白4F2hc和LAT 1的水平分别与足月对照和早产（早孕对照）相比显著升高（p < 0.05）。与足月对照组相比，IUGR胎盘中升高的mTOR蛋白独特地更高（P = 0.0026）。总细胞ASCT2转运蛋白水平在所有组中相似，然而，定位于ST微绒毛膜（MVM）的ASCT2蛋白水平在IUGR中显著低于足月妊娠和早产妊娠（分别为P = 0.0006，0.03）。此外，ASCT2和mTOR蛋白水平与母亲孕前BMI呈正相关（分别为P = 0.046，0.048）。基于本研究，有三个重要发现。首先，在营养物质可用性有限的条件下，如PE或IUGR，ST中System L和mTOR蛋白表达水平总体增加，提示适应性反应。其次，ST MVM处ASCT 2蛋白的减少表明翻译后事件可能会降低IUGR胎盘中的AAT活性。第三，基于ASCT2和mTOR表达值观察到的正相关性，提出转运蛋白表达和孕前BMI之间的生理联系。
Sufficient amino acid transport activity (AAT) is indispensable for appropriate fetal growth. Studies suggest that placental nutrient uptake activity is responsive to both maternal and fetal nutrient demands. We hypothesize that under conditions of limited nutrient availability to the fetus, as often present in preeclampsia, intrauterine growth restriction (IUGR), and insufficient weight-gain during pregnancy, a general adaptive response aimed to increase amino acid transport activity may be observed in the placenta. A total of 40 placentas from full-term (n = 10) and pre-term (average gestational period = 34.8 weeks, n = 10) normal pregnancies, IUGR (n = 10), and preeclampsia (n = 10) associated pregnancies were looked at by immunohistochemistry followed by relative qualitative scoring to compare expression levels and localization of System L, ASCT2, and mTOR proteins. Microvillous syncytiotrophoblast (ST) in placenta of pregnancies complicated by IUGR or preeclampsia (PE) showed significant increases in the levels of System L amino acid transport proteins 4F2hc and LAT1 compared to both full-term control and pre-term (early gestation control) pregnancies seperately (p < 0.05). Elevated mTOR protein was uniquely higher in IUGR placentas compared to full-term controls (P = 0.0026). Total cellular ASCT2 transporter protein levels were similar in all groups, however, levels of ASCT2 protein localized to the ST microvillous membrane (MVM) were significantly lower in IUGR compared to both full-term and pre-term pregnancies (P = 0.0006, 0.03, respectively). Additionally, ASCT2 and mTOR protein levels were positively associated with maternal pre-pregnancy BMI (P = 0.046, 0.048, respectively). There are three important findings based upon the present study. First, in conditions of limited nutrient availability, such as PE or IUGR, there is an overall increase in the level of System L and mTOR protein expression in the ST, suggestive of an adaptive response. Second, a decrease in ASCT2 protein at the ST MVM suggests a post-translational event that may decrease AAT activity in IUGR placentas. Third, a physiological link between transporter expression and pre-pregnancy BMI is suggested based upon a positive association observed with ASCT2 and mTOR expression values.
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影响因子：
5.5
作者：
Coan, P. M.;Vaughan, O. R.;Fowden, A. L.
通讯作者：
Fowden, A. L.
影响因子：
5.5
作者：
Fuchs, Bryan C.;Finger, Richard E.;Bode, Barrie P.
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作者：
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DOI：
10.1111/j.1471-0528.2005.00843.x
发表时间：
2006-02-01
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作者：
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DOI：
10.1152/ajpgi.00344.2003
发表时间：
2004-03-01
影响因子：
4.5
作者：
Fuchs, BC;Perez, JC;Bode, BP
通讯作者：
Bode, BP