Characterization and distribution of ferritin binding sites in the adult mouse brain

Studies on iron uptake into the brain have traditionally focused on transpo rt by transferrin. However, transferrin receptors are not found in all brai n regions and are especially low in white matter tracts where high iron con centrations have been reported. Several lines of research suggest that a re ceptor for ferritin, the intracellular storage protein for iron, may exist. We present, herein, evidence for ferritin binding sites in the brains of a dult mice. Autoradiographic studies using I-125-recombinant human ferritin demonstrate that ferritin binding sites in brain are predominantly in white matter. Saturation binding analyses revealed a single class of binding sit es with a dissociation constant (K-D) of 4.65 x 10(-9) M and a binding site density (B-max) of 17.9 fmol bound/mu g of protein. Binding of radiolabele d ferritin can be competitively displaced by an excess of ferritin but not transferrin. Ferritin has previously been shown to affect cellular prolifer ation, protect cells from oxidative damage, and deliver iron. The significa nce of a cellular ferritin receptor is that ferritin is capable of deliveri ng 2,000 times more iron per mole of protein than transferrin. The distribu tion of ferritin binding sites in brain vis-a-vis transferrin receptor dist ribution suggests distinct methods for iron delivery between gray and white matter.