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

被引:70
作者
Hulet, SW
Hess, EJ
Debinski, W
Arosio, P
Bruce, K
Powers, S
Connor, JR [1 ]
机构
[1] Penn State Univ, Milton S Hershey Med Ctr, Dept Anat & Neurosci,Coll Med, George M Leader Family Lab Alzheimers Dis Res, Hershey, PA 17033 USA
[2] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Neurosurg, Hershey, PA 17033 USA
[3] Univ Brescia, HS Raffaele, Dipartimento Ric Biol & Technol, Inst Ric & Cura Carattere Sci, Milan, Italy
关键词
ferritin binding sites; myelin; transferrin; white matter; ferritin receptor; iron delivery; oligodendrocytes; mouse brain;
D O I
10.1046/j.1471-4159.1999.720868.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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 sites 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 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-a-vis transferrin receptor distribution suggests distinct methods for iron delivery between gray and white matter.
引用
收藏
页码:868 / 874
页数:7
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