ZINC METABOLISM IN HUMAN TROPHOBLAST CELLS

人类滋养层细胞中的锌代谢

• 批准号: 3328299
• 负责人: BO L LONNERDAL
• 金额: $ 9.91万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3328299
• 关键词: human tissue; macroglobulins; metal metabolism; metallothionein; mother /embryo /fetus nutrition; nutrition related tag; placental transfer; radiotracer; serum albumin; tissue /cell culture; trophoblast; zinc

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.

人类胎儿取决于足够的锌供应 实现正常的产后和产后发展。 由于其位置， 胎盘，尤其是胎盘滋养细胞，必须玩 至关重要的作用在将母锌传递到胎儿中。 该提议的主要长期目标是获得一些 了解涉及胎盘运输的细胞机制 胎儿的母锌。 在血浆中，发现锌大多相关 与白蛋白和α2M一起使用。 因此，在第一个具体目的中，我们提出 将生化和形态学技术的结合与 评估流体相和吸附性内吞作用在摄取中的作用 以及α2M和白蛋白的加工。 在第二个特定目标中，我们将 以与 α2M和白蛋白，并确定细胞内的因素和细胞内 分离和后续处理涉及的隔室 蛋白质结合的锌。 第三个特定目标将调查动力学 和控制锌释放的控制，并试图发现的化学形式 释放的金属。 这三个特定目标应共同提供 有关锌涉及的细胞机制的重要新信息 滋养细胞的吸收和代谢。 在特定目标四中，我们将学习 锌对控制α2M受体表达的影响，因为 表达的变化可能会对细胞内锌水平和 在锌运输上。 在最后一个特定目标中，我们将研究 滋养细胞代谢中的金属硫蛋白。 金属硫蛋白已经过去了 与许多系统中的锌稳态控制有关。 我们 在体外分化过程中也将检查金属硫硫蛋白水平 作为测量金属硫蛋白合成和降解的速率。