Fleming J T, Joshi J G
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
Neurobiol Aging. 1991 Sep-Oct;12(5):413-8. doi: 10.1016/0197-4580(91)90066-s.
We previously showed that human brain ferritin (HBF) binds aluminum (Al) in vivo and in vitro and HBF isolated from Alzheimer's brain had more Al bound compared to aged matched controls (7). To further understand the role ferritin may play in Al neurotoxicity, we have studied in vitro the effect of Al on the function of human ferritin isolated from Alzheimer's (AD) and normal brain tissue, and compared the results with other mammalian ferritins. Al causes a concentration-dependent decrease in the initial rate of iron loading into apo-horse spleen and human brain ferritin and the rates were similar for ferritin isolated from both AD and normal brains. The rates of iron release of mammalian ferritins from different tissues were determined: horse spleen much greater than human liver greater than rat brain greater than human brain = rat liver ferritin. The rates of iron release of AD and normal human brain ferritin were similar and were unaffected by preloading with Al. Several mammalian ferritins were compared for their total iron uptake: horse spleen = human liver greater than human brain (normal) = human brain (AD) ferritin. In 20 mM HEPES (pH 6.0) buffer holoferritin is more resistant to precipitation by Al than apoferritin suggesting that holoferritin is a better chelator for nonferrous metal ions.
我们之前的研究表明，人脑铁蛋白（HBF）在体内和体外均能结合铝（Al），并且与年龄匹配的对照组相比，从阿尔茨海默病患者大脑中分离出的HBF结合的铝更多（7）。为了进一步了解铁蛋白在铝神经毒性中可能发挥的作用，我们在体外研究了铝对从阿尔茨海默病（AD）和正常脑组织中分离出的人铁蛋白功能的影响，并将结果与其他哺乳动物铁蛋白进行了比较。铝导致脱铁马脾铁蛋白和人脑铁蛋白中铁加载初始速率呈浓度依赖性下降，并且从AD脑和正常脑中分离出的铁蛋白的速率相似。测定了不同组织来源的哺乳动物铁蛋白的铁释放速率：马脾铁蛋白远大于人肝铁蛋白大于大鼠脑铁蛋白大于人脑铁蛋白 = 大鼠肝铁蛋白。AD人脑铁蛋白和正常脑铁蛋白的铁释放速率相似，且不受铝预加载的影响。比较了几种哺乳动物铁蛋白的总铁摄取量：马脾铁蛋白 = 人肝铁蛋白大于人脑（正常）铁蛋白 = 人脑（AD）铁蛋白。在20 mM HEPES（pH 6.0）缓冲液中，全铁蛋白比脱铁蛋白更耐铝沉淀，这表明全铁蛋白是更好的有色金属离子螯合剂。
