ZINC METABOLISM IN HUMAN TROPHOBLAST CELLS

人类胎儿依赖于充足的锌供应， 实现正常的产前和产后发育。 因为它的位置， 胎盘，特别是胎盘滋养层，必须发挥作用， 在母体向胎儿提供锌方面起着至关重要的作用。 这项建议的主要长期目标是， 了解胎盘运输的细胞机制， 母体锌对胎儿的影响 在血浆中，锌主要与 白蛋白和α 2M 因此，在第一个具体目标中，我们提出 结合生物化学和形态学技术， 评价液相和吸附性内吞在摄取中的作用 以及α 2M和白蛋白的加工。 在第二个具体目标中， 研究锌的吸收和加工， α 2M和白蛋白，并确定因子和细胞内 参与解离和随后的处理的隔室 蛋白结合锌 第三个具体目标将研究动力学 和控制锌的释放，并试图发现的化学形式， 释放的金属。 这三个具体目标应共同提供 关于锌参与的细胞机制的重要新信息 通过滋养层吸收和代谢。 在具体目标四中，我们将研究 锌对α 2M受体表达的控制作用， 表达的变化可能对细胞内锌水平产生影响， 锌的运输。 在最后一个具体目标中，我们将研究 金属硫蛋白在滋养层锌代谢中的作用。 金属硫蛋白一直是 在许多系统中涉及锌稳态的控制。 我们 将在体外分化过程中检测金属硫蛋白水平 作为测量金属硫蛋白合成和降解的速率。

The human fetus is dependent on an adequate supply of zinc in order to achieve normal pre- and postnatal development. Because of its location, the placenta, and in particular, the placental trophoblast, must play a critically important role in the delivery of maternal zinc to the fetus. The major long-term objective of this proposal is to gain some understanding of the cellular mechanism involved in placental transport of maternal zinc to the fetus. In plasma, zinc is mostly found associated with albumin and alpha2M. Therefore, in the first specific aim we propose to use a combination of biochemical and morphological techniques to evaluate the roles of fluid-phase and adsorptive endocytosis in the uptake and processing of alpha2M and albumin. In the second specific aim we will study the uptake and processing of zinc in the form of complexes with alpha2M and albumin and to determine the factors and intracellular compartments involved in the dissociation and subsequent processing of protein-bound zinc. The third specific aim will investigate the kinetics and control of zinc release and attempt to discover the chemical form of the released metal. Together, these three specific aims should provide important new information on the cellular mechanisms involved in zinc uptake and metabolism by trophoblast. In specific aim four we will study the effects of zinc on the control of alpha2M receptor expression since changes in expression could have an effect on intracellular zinc levels and on zinc transport. In the last specific aim we will study the role of metallothionein in trophoblast zinc metabolism. Metallothionein has been implicated in the control of zinc homeostasis in a number of systems. We will examine metallothionein levels during differentiation in vitro as well as measuring rates of metallothionein synthesis and degradation.