title: Accelerated transferrin degradation in HFE-deficient mice is associated with increased transferrin saturation.
abstract: 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.
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chaity
authors.initials: C
authors.lastname: Chaudhury
authors.forename: Jonghan
authors.initials: J
authors.lastname: Kim
authors.forename: Samina
authors.initials: S
authors.lastname: Mehnaz
authors.forename: Manzoor A
authors.initials: MA
authors.lastname: Wani
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Oberyszyn
authors.forename: C L
authors.initials: CL
authors.lastname: Bronson
authors.forename: Sudhasri
authors.initials: S
authors.lastname: Mohanty
authors.forename: William L
authors.initials: WL
authors.lastname: Hayton
authors.forename: John M
authors.initials: JM
authors.lastname: Robinson
authors.forename: Clark L
authors.initials: CL
authors.lastname: Anderson
mesh_terms: D000821:Animal Feed; D000818:Animals; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D007070:Immunoglobulin A / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011507:Proteinuria; D012016:Reference Values; D014168:Transferrin / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D007070:Immunoglobulin A; D008565:Membrane Proteins; D014168:Transferrin