The transferrin homologue, melan transferrin (p97), is rapidly catabolized by the liver of the rat anal 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 Fe-59-I-125-sMTf and compared it to Fe-59-I-125-Tf that were injected intravenously in rats. Studies were also performed to measure Fe-59 and I-125-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 Fe-59 was largely retained by these organs but the I-125 was released into the plasma. Only a small amount of I-125-sMTf or its bound Fe-59 was taken up by the brain, less than that from Fe-59-I-125-Tf. There was much less Fe-59 uptake by erythropoietic organs (spleen and femurs) from Fe-59-sMTf than from Fe-59-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. (C) 2004 Elsevier B.V. All rights reserved.