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Publication : Accelerated transferrin degradation in HFE-deficient mice is associated with increased transferrin saturation.

First Author  Chaudhury C Year  2006
Journal  J Nutr Volume  136
Issue  12 Pages  2993-8
PubMed ID  17116709 Mgi Jnum  J:117735
Mgi Id  MGI:3697526 Doi  10.1093/jn/136.12.2993
Citation  Chaudhury C, et al. (2006) Accelerated transferrin degradation in HFE-deficient mice is associated with increased transferrin saturation. J Nutr 136(12):2993-8
abstractText  HFE, a major histocompatibility complex class I-related protein, is implicated in the iron overload disease, hereditary hemochromatosis. Whereas patients with hereditary hemochromatosis have low serum transferrin levels, little is known about transferrin turnover in HFE deficiency states. We injected mice intravenously with radioiodinated transferrin and compared plasma transferrin decay and steady-state endogenous transferrin concentration in the plasma between HFE-deficient and wild-type C57BL/6 mouse strains. HFE-deficient mice degraded transferrin faster than normal (P < 0.001) and had lower plasma transferrin concentrations (P < 0.001). Both HFE-deficient and wild-type mice were then fed diets with 3 different iron concentrations that we designated deficient (2-5 mg/kg of iron), control (0.2 g/kg), and overload (20 g/kg) for 6 wk immediately after weaning to create a range of serum iron concentrations and resultant transferrin saturations ranging from 16 to 78%. We found an inverse correlation between transferrin saturation and transferrin half-life (P < 0.0001, r = -0.839) for both HFE-deficient and wild-type mice, which suggests that HFE does not have a direct effect on transferrin catabolism; rather, HFE may influence transferrin half-life indirectly through its effect on transferrin saturation, which in turn enhances transferrin decay in HFE-deficient mice.
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