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Brain capillary endothelial cells mediate iron transport into the brain by segregating iron from transferrin without the involvement of divalent metal transporter 1
Author(s) -
Moos Torben,
Skjoerringe Tina,
Gosk Sara,
Morgan Evan H.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04023.x
Subject(s) - dmt1 , transferrin , transferrin receptor , transporter , ferrous , chemistry , divalent , biochemistry , biology , medicine , endocrinology , microbiology and biotechnology , gene , organic chemistry
Rats were studied for [ 59 Fe‐ 125 I]transferrin uptake in total brain, and fractions containing brain capillary endothelial cells (BCECs) or neurons and glia. 59 Fe was transported through BCECs, whereas evidence of similar transport of transferrin was questionable. Intravenously injected transferrin localized to BCECs and failed to accumulate within neurons, except near the ventricles. No significant difference in [ 125 I]transferrin distribution was observed between Belgrade b/b rats with a mutation in divalent metal transporter I (DMT1), and Belgrade +/b rats with regard to accumulation in vascular and postvascular compartments. 59 Fe occurred in significantly lower amounts in the postvascular compartment in Belgrade b/b rats, indicating impaired iron uptake by transferrin receptor and DMT1‐expressing neurons. Immunoprecipitation with transferrin antibodies on brains from Belgrade rats revealed lower uptake of transferrin‐bound 59 Fe. In postnatal (P)0 rats, less 59 Fe was transported into the postvascular compartment than at later ages, suggesting that BCECs accumulate iron at P0. Supporting this notion, an in situ perfusion technique revealed that BCECs accumulated ferrous and ferric iron only at P0. However, BCECs at P0 together with those of older age lacked DMT1. In conclusion, BCECs probably mediate iron transport into the brain by segregating iron from transferrin without involvement of DMT1.