Identification of a novel route of iron transcytosis across the mammalian blood-brain barrier.
OBJECTIVE
This study was undertaken to assess the role of p97 (also known as melanotransferrin) in the transfer of iron into the brain, because the passage of most large molecules is limited by the presence of the blood-brain barrier, including that of the serum iron transporter transferrin.


METHODS
To study the function of the soluble form of p97, we followed the uptake of radioiodinated and 55Fe loaded p97 and transferrin by the brain during a 24-hour period.


RESULTS
We show that the soluble form of p97 has the ability to transcytose across the murine blood-brain barrier, and its transcytosis can be inhibited in a specific manner. We also provide evidence that p97 transports iron into the brain more efficiently than transferrin.


CONCLUSIONS
These data support the idea that p97 is an important iron transporter across the blood-brain barrier in normal physiology and possibly in neurodegenerative diseases, such as Alzheimer disease, in which iron homeostasis in the brain becomes disrupted.
Moroo
Iku
I
Biotechnology Laboratory, University of British Columbia, Vancouver, Canada.
Ujiie
Maki
M
Walker
Brandie L
BL
Tiong
Jacqueline W C
JW
Vitalis
Timothy Z
TZ
Karkan
Delara
D
Gabathuler
Reinhard
R
Moise
Alexander R
AR
Jefferies
Wilfred A
WA
D000818:Animals; D000951:Antigens, Neoplasm; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000493:pharmacokinetics*; D014168:Transferrin / Q000493:pharmacokinetics
D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014168:Transferrin; D007501:Iron