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Studies on iron uptake into the brain have traditionally focused on transport by transferrin. However, transferrin receptors are not found in all brain regions and are especially low in white matter tracts where high iron concentrations have been reported. Several lines of research suggest that a receptor for ferritin, the intracellular storage protein for iron, may exist. We present, herein, evidence for ferritin binding sites in the brains of adult mice. Autoradiographic studies using 125 Irecombinant human ferritin demonstrate that ferritin binding sites in brain are predominantly in white matter. Saturation binding analyses revealed a single class of binding sites with a dissociation constant (K D ) of 4.65 ϫ 10 Ϫ9 M and a binding site density (B max ) of 17.9 fmol bound/ g of protein.Binding of radiolabeled ferritin can be competitively displaced by an excess of ferritin but not transferrin. Ferritin has previously been shown to affect cellular proliferation, protect cells from oxidative damage, and deliver iron. The significance of a cellular ferritin receptor is that ferritin is capable of delivering 2,000 times more iron per mole of protein than transferrin. The distribution of ferritin binding sites in brain vis-à -vis transferrin receptor distribution suggests distinct methods for iron delivery between gray and white matter. Key Words: Ferritin binding sites-Myelin-Transferrin-White matter-Ferritin receptor-Iron delivery-Oligodendrocytes-Mouse brain.

Cationic selena- and tellurapyrylium dyes 1d-g and 1i were found to inhibit cytochrome c oxidase upon irradiation of isolated mitochondrial suspensions treated with 10 microM solutions of dye. The amount of inhibition by these dyes was found to be related to oxygen concentration and inversely related to the concentration of added imidazole, a singlet-oxygen trap, suggesting that singlet oxygen is responsible, at least in part, for the inhibition of the enzyme. Dyes 1d-g and 1i, containing either selenium or tellurium, produce singlet oxygen with a quantum efficiency, phi (1O2), between 0.005 and 0.09 in methanol. Dyes 1a-c, containing the lighter chalcogens oxygen and sulfur, have values of phi (1O2) that are less than 0.0008 in methanol and do not inhibit cytochrome c oxidase in irradiated mitochondrial suspensions. Dyes 1c and 1d have nearly identical spectral and redox properties. Only the selenapyrylium dye 1d inhibits the enzyme, suggesting that neither ground-state nor excited-state electron transfer is important in inhibition of the enzyme. Electron micrographs of human U251 glioma cells, treated in vitro with 1i and light, showed pronounced morphology changes in the mitochondrial membranes relative to electron micrographs of untreated cells. Epifluorescence microscopy of the treated cells showed granular yellow-green fluorescence presumably from photooxidized dye in the mitochondria.

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