The transferrin homologue, melanotransferrin (p97), is rapidly catabolized by the liver of the rat and does not effectively donate iron to the brain.
Melanotransferrin (MTf) or melanoma tumor antigen p97 is a membrane-bound transferrin (Tf) homologue that binds iron (Fe). This protein is also found as a soluble form in the plasma (sMTf) and was suggested to be an Alzheimer's disease marker. In addition, sMTf has been recently suggested to cross the blood-brain barrier (BBB) and accumulate in the brain of the mouse following intravenous infusion. Considering the importance of this observation to the physiology and pathophysiology of the BBB and the function of sMTf in vivo, we investigated the uptake and distribution of 59Fe-125I-sMTf and compared it to 59Fe-125I-Tf that were injected intravenously in rats. Studies were also performed to measure 59Fe and 125I-protein uptake by reticulocytes using these radiolabelled proteins. The results showed that sMTf was rapidly catabolized, mainly in the liver and to a lesser extent by the kidneys. The 59Fe was largely retained by these organs but the 125I was released into the plasma. Only a small amount of 125I-sMTf or its bound 59Fe was taken up by the brain, less than that from 59Fe-125I-Tf. There was much less 59Fe uptake by erythropoietic organs (spleen and femurs) from 59Fe-sMTf than from 59Fe-Tf, and no evidence of receptor-mediated uptake of sMTf was obtained using reticulocytes. It is concluded that compared to Tf, sMTf plays little or no role in Fe supply to the brain and erythropoietic tissue. However, a small amount of sMTf was taken up from the plasma by the brain and a far greater amount by the liver.
Children's Cancer Institute Australia for Medical Research, Iron Metabolism and Chelation Program, PO Box 81, High Street, Randwick, Sydney, New South Wales 2031. d.richardson@ccia.org.au
Des R
DR
Richardson
Evan H
EH
Morgan
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000951:Antigens, Neoplasm; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047468:Immunoprecipitation; D007457:Iodine Radioisotopes / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism; D058950:Melanoma-Specific Antigens; D051379:Mice; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012156:Reticulocytes / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000737:chemistry
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014168:Transferrin; D007501:Iron