Dedman D J, Treffry A, Candy J M, Taylor G A, Morris C M, Bloxham C A, Perry R H, Edwardson J A, Harrison P M
Department of Molecular Biology and Biotechnology, University of Sheffield, U.K.
Biochem J. 1992 Oct 15;287 ( Pt 2)(Pt 2):509-14. doi: 10.1042/bj2870509.
Ferritin has been isolated and its subunit composition, iron and aluminium content determined in the cerebral cortex and cerebellum of normal individuals and in the cerebral cortex of Alzheimer's-disease and renal-dialysis patients. An e.l.i.s.a. for ferritin has been developed and the ferritin, non-haem iron and aluminium content of the parietal cortex were determined in normal individuals and Alzheimer's-disease patients. It was found that ferritin from the cerebral cortex and cerebellum of normal individuals had a high H-subunit content, similar to that of heart ferritin. The subunit composition of ferritin isolated from the cerebral cortex was not significantly altered in Alzheimer's-disease or renal-dialysis patients. Ferritin from the cerebral cortex of normal individuals had only approx. 1500 atoms of iron per molecule and the iron content of ferritin was not significantly changed in Alzheimer's-disease or renal-dialysis patients. Ferritin isolated from the cerebral cortex of normal, Alzheimer's-disease and renal-dialysis patients had less than 9 atoms of aluminium per molecule. The failure to find increased concentrations of aluminium associated with ferritin in dialysis patients, who had markedly increased concentrations of aluminium in the cerebral cortex, shows that aluminium does not accumulate in ferritin in vivo. This has important implications for the toxicity of aluminium, since it implies that cells are unable to detoxify aluminium by the same mechanism as that available for iron. Comparison of the concentrations of ferritin, aluminium and iron in the parietal cortex from normal and Alzheimer's-disease patients showed that, whereas the concentration of aluminium was not increased, both ferritin and iron were significantly increased in Alzheimer's disease.
已从正常个体的大脑皮质和小脑中以及阿尔茨海默病患者和肾透析患者的大脑皮质中分离出铁蛋白,并测定了其亚基组成、铁和铝含量。已开发出一种用于铁蛋白的酶联免疫吸附测定法,并测定了正常个体和阿尔茨海默病患者顶叶皮质中的铁蛋白、非血红素铁和铝含量。结果发现,正常个体大脑皮质和小脑中的铁蛋白具有较高的H亚基含量,类似于心脏铁蛋白。从大脑皮质分离出的铁蛋白的亚基组成在阿尔茨海默病或肾透析患者中没有明显改变。正常个体大脑皮质中的铁蛋白每个分子仅约有1500个铁原子,并且铁蛋白的铁含量在阿尔茨海默病或肾透析患者中没有明显变化。从正常、阿尔茨海默病和肾透析患者的大脑皮质中分离出的铁蛋白每个分子的铝含量少于9个原子。在大脑皮质中铝浓度明显升高的透析患者中,未发现与铁蛋白相关的铝浓度增加,这表明铝在体内不会在铁蛋白中积累。这对铝的毒性具有重要意义,因为这意味着细胞无法通过与铁相同的机制来解毒铝。比较正常和阿尔茨海默病患者顶叶皮质中铁蛋白、铝和铁的浓度表明,虽然铝浓度没有增加,但在阿尔茨海默病中铁蛋白和铁均显著增加。