PLACENTAL VITAMIN TRANSPORT-MOLECULAR & CELLULAR ASPECTS

描述：(改编自调查人员摘要)：SMVT是一个运输者 当它在哺乳动物细胞中表达时，会诱导 泛酸、生物素和脂酸盐。由于SMVT介导生物素的摄取 在肠道和胎盘中，研究人员都假设 胎盘中SMVT的表达也受血浆的调节 生物素、泛酸和脂酸盐的浓度。这将在 BeWo绒毛膜癌细胞和妊娠大鼠的体内外研究 模型系统。研究将包括对运输变化的分析 活跃度、转运体密度和转运体的稳态水平 由泛酸、生物素和生物素浓度变化诱导的mRNA 培养基或母体血浆中的脂类。免疫定位研究 将用于检测克隆的转运蛋白在 刷取合体滋养层细胞边缘和/或基底膜以了解 SMVT在胎盘维生素进入和/或排出中的作用。这个 将研究转运蛋白在胎盘和胎儿中的个体发育 以大鼠为动物模型。两个分子的详细功能描述 维生素C转运体，SVCTI和SVCT2，被建议用来确定 中呈现此传输器特定表达式的SVCT2函数 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SVCT2表达的调节 大鼠胎盘和BeWo细胞对底物可利用性和个体发生的响应 SVCT2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.