PLACENTAL VITAMIN TRANSPORT-MOLECULAR & CELLULAR ASPECTS

描述：（改编自研究者摘要）：SMVT是一种转运蛋白 当在哺乳动物细胞中表达时， 泛酸、生物素和硫辛酸。由于SMVT介导生物素的摄取， 在肠和胎盘中，研究者假设 胎盘中SMVT的表达也受到血浆中 生物素、泛酸盐和硫辛酸盐的浓度。这将在 以BeWo绒毛膜癌细胞和孕鼠为研究对象， 模型系统研究将包括分析运输的变化， 活性、转运蛋白密度和转运蛋白的稳态水平 通过泛酸、生物素和 培养基或母体血浆中的脂肪酸盐。免疫定位研究 将进行检查克隆的转运蛋白在 刷状缘和/或基底膜的合体滋养层，以了解 SMVT在维生素进入和/或离开胎盘中的作用。的 将研究胎盘和胎儿中转运蛋白的个体发育 用老鼠做动物模型。两个详细的功能特性 维生素C转运蛋白，SVCT 1和SVCT 2，提出确定的特点， SVCT 2功能，使该转运蛋白在细胞中特异性表达， 胎盘更有利于维生素C的经胎盘转运。 拟议的研究还将调查SVCT 2表达的调控， 大鼠胎盘和BeWo细胞对底物利用和个体发育的反应 SVCT 2在大鼠胎盘中的发育。

DESCRIPTION: (Adapted from the Investigator's Abstract): SMVT is a tranporter which, when expressed in mammalian cells, induces the transport of pantothenate, biotin, and lipoate. Since SMVT mediates the uptake of biotin both in the intestine and the placenta, the investigator hypothesizes that the expression of SMVT in the placenta is also subject to regulation by plasma concentrations of biotin, pantothenate and lipoate. This will be tested in vitro and in vivo using BeWo choriocarcinoma cells and the pregnant rat as model systems. Studies will include analysis of changes in the transport activity, transporter density, and the steady-state levels of the transporter mRNA induced by changes in the concentrations of pantothenate, biotin, and lipoate in the culture medium or maternal plasma. Immunolocalization studies will be performed to examine the expression of the cloned transporter in the brush border and/or basal membrane of the syncytiotrophoblast to understand the role of SMVT in the entry and/or exit of the vitamins in the placenta. The ontogenic development of the transporter in placenta and fetus will be studied using rats as an animal model. A detailed functional characterization of two vitamin C transporters, SVCTI and SVCT2, is proposed to determine features of SVCT2 function that render the specific expression of this transporter in the placenta more advantageous for the transplacental transfer of vitamin C. Proposed studies will also investigate the regulation of SVCT2 expression in rat placenta and BeWo cells in response to substrate availability and ontogenic development of SVCT2 in rat placenta.