Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis

Journal Article · Fri May 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.10.3457· OSTI ID:5551826

Craven, C M; Alexander, J; Eldridge, M; Kushner, J P; Bernstein, S; Kaplan, J

Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decrease plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is clear by the parenchymal tissues, the tissue distribution of /sup 59/Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congential hypotransferrinemia. In control animals, injected /sup 59/Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected /sup 59/Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound /sup 59/Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected /sup 59/Fe was removed with a half-time of <30 s. Analysis of the distribution of /sup 59/Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of /sup 59/Fe not bound to transferrin. These results demonstrate the existence of and uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is consequence of reduced concentrations of apotransferrin.

• Research Organization: Univ. of Utah College of Medicine, Salt Lake
• OSTI ID: 5551826
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:10; ISSN PNASA
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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CHLORINE COMPOUNDS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
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ENDOCRINE GLANDS
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LIVER
MAMMALS
MATERIALS
METALLOPROTEINS
MICE
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PROTEINS
RADIOISOTOPES
RADIONUCLIDE KINETICS
RODENTS
TISSUE DISTRIBUTION
TRANSFERRIN
TRANSITION ELEMENT COMPOUNDS
UPTAKE
VERTEBRATES