RECEPTOR-MEDIATED UPTAKE OF IRON FROM LACTOFERRIN

  • Lonnerdal, Bo, (PI)

Project: Research project

Project Details

Description

DESCRIPTION It is well-known that the
bioavailability of iron from human milk is very high. The investigators
have hypothesized that this high bioavailability is the result of a
receptor-mediated mechanism in the small intestine that facilitates the
absorption of iron from LF, the major iron-binding protein in human milk.
Preliminary data demonstrate the presence of a specific LFR in the small
intestinal brush border membrane of human infants and piglets. In the
proposed project, the investigators intend to isolate and characterize the
human LFR with regard to molecular size, isoelectric point, subunit
arrangement, amino acid and carbohydrate composition and to study the
molecular interaction between LF and the LFR. A polyclonal antibody
towards LFR will be developed and the gene will be cloned from a human
small intestinal cDNA library in lamda-gt11. The gene will be sequenced
and the amino acid sequence deduced from the nucleotide sequence. In
parallel experiments, the pig LFR will be characterized, an antibody
produced and the LFR gene cloned and sequenced. The piglet will then be
used as an animal model to study the ontogeny of the LFR, the localization
in the small intestine and the effect of iron status on the concentrations
of LFR and its mRNA, using the isolated cDNA as a probe. Using piglet
enterocytes in suspension, the potential internalization of Lf and LfR will
be studied. In conclusion, the results from this proposal should provide a
detailed insight into the molecular nature of the LFR, its interaction with
LF and the mechanism of iron uptake into the enterocyte. Information on
the ontogeny of the LFR, localization in the gut and the effect of iron
status on LFR expression will be obtained from the animal model chosen.
StatusFinished
Effective start/end date5/1/914/30/97

Funding

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

ASJC

  • Medicine(all)

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