Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis
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), Vol. 84:10
- Country of Publication:
- United States
- Language:
- English
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BLOOD PLASMA
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IRON 59
INTESTINAL ABSORPTION
TISSUE DISTRIBUTION
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BIOLOGICAL MODELS
BLOOD
ELECTROPHORESIS
HEREDITARY DISEASES
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DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DISTRIBUTION
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
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GLOBULINS
GLOBULINS-BETA
HALIDES
HALOGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
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IRON ISOTOPES
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MAMMALS
MATERIALS
METALLOPROTEINS
NUCLEI
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