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Ferroportin deficiency impairs manganese metabolism in flatiron mice
Author(s) -
Seo Young Ah,
WesslingResnick Marianne
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-262592
Subject(s) - ferroportin , manganese , metabolism , chemistry , mutant , bioavailability , medicine , wild type , microbiology and biotechnology , endocrinology , biochemistry , biology , gene , pharmacology , iron homeostasis , organic chemistry
We examined the physiologic role of ferroportin (Fpn) in manganese (Mn) export using flatiron ( ffe /+) mice, a genetic model of Fpn deficiency. Blood (0.0123 vs . 0.0107 mg/kg; P = 0.0003), hepatic (1.06 vs . 0.96 mg/kg; P = 0.0125), and bile Mn levels (79 vs. 38 mg/kg; P = 0.0204) were reduced in ffe /+ mice compared to +/+ controls. Erythrocyte Mn‐superoxide dismutase was also reduced at 6 (0.154 vs . 0.096, P = 0.0101), 9 (0.131 vs . 0.089, P = 0.0162), and 16 weeks of age (0.170 vs. 0.090 units/mg protein/min; P < 0.0001). 54 Mn uptake after intragastric gavage was markedly reduced in ffe /+ mice (0.0187 vs . 0.0066% dose; P = 0.0243), while clearance of injected isotope was similar in ffe /+ and +/+ mice. These values were compared to intestinal absorption of 59 Fe, which was significantly reduced in ffe /+ mice (8.751 vs . 3.978% dose; P = 0.0458). The influence of the ffe mutation was examined in dopaminergic SH‐SY5Y cells and human embryonic HEK293T cells. While expression of wild‐type Fpn reversed Mn‐induced cytotoxicity, ffe mutant H32R failed to confer protection. These combined results demonstrate that Fpn plays a central role in Mn transport and that flatiron mice provide an excellent genetic model to explore the role of this exporter in Mn homeostasis.— Seo, Y. A., Wessling‐Resnick, M. Ferroportin deficiency impairs manganese metabolism in flatiron mice. FASEB J . 29, 2726‐2733 (2015). www.fasebj.org