ZINC METABOLISM IN HUMAN TROPHOBLAST CELLS

  • Lonnerdal, Bo, (PI)

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date2/1/927/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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