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Olfactory manganese uptake in Hfe knockout mice, a model of iron overload
Author(s) -
Kim Jonghan,
Wessling-Resnick Marianne
Publication year - 2012
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/fasebj.26.1_supplement.641.11
Subject(s) - dmt1 , olfactory epithelium , chemistry , hemochromatosis , hereditary hemochromatosis , endocrinology , neurotoxicity , transporter , olfactory bulb , knockout mouse , ferroportin , nasal administration , medicine , homeostasis , olfactory mucosa , olfactory system , metabolism , biochemistry , pharmacology , toxicity , iron homeostasis , biology , central nervous system , receptor , neuroscience , organic chemistry , gene
Iron deficiency increases dietary Fe absorption due to up‐regulation of divalent metal transporter‐1 (DMT1) in intestinal epithelium. DMT1 also transports Mn and we have shown iron deficiency enhances olfactory Mn uptake to the brain due to iron‐responsive regulation of DMT1 in olfactory epithelium. Understanding the influence of iron homeostasis on olfactory Mn uptake is important due to the neurotoxicity of airborne metal. Whether iron loading alters olfactory Mn uptake is unknown. Hereditary hemochromatosis, an iron overload disease associated with excessive intestinal Fe absorption, is commonly caused by loss of HFE gene function. We have characterized Mn pharmacokinetics in Hfe knockout mice after intravenous and intranasal 54 Mn administration. Hfe − / − mice had higher serum and liver iron than Hfe +/+ mice, consistent with iron overload status. In contrast, Hfe − / − mice displayed lower blood Mn levels. After intravenous injection, Hfe − / − mice cleared 54 Mn from the blood more rapidly than Hfe +/+ mice while 54 Mn distribution to the brain was similar. However, after intranasal instillation 54 Mn brain levels in Hfe − / − mice were elevated indicating olfactory uptake to the brain is enhanced by iron loading. The possible role of DMT1 and other metal transporters in enhanced olfactory Mn absorption to the brain due to HFE‐associated iron loading should be further studied. Supported by NIH DA027030 and ES017781. Grant Funding Source : NIH