ALUMINUM TAKEN UP BY TRANSFERRIN-INDEPENDENT IRON UPTAKE AFFECTS THE IRON-METABOLISM IN RAT CORTICAL-CELLS

We previously demonstrated that cultured human fibroblasts internalize iron via transferrin-independent iron uptake (Tf-IU), redox, and rece ptor-mediated endocytosis uptake systems [Oshiro, S., Nakajima, H., Ma rkello, T., Krasnewich, D., Bernardini, I., and Gahl, W.A. (1993) J, B iol. Chem. 268, 21586-21591], Of these iron transport systems, the Tf- IU system is involved in the accumulation of transition metals in vari ous mammalian cells. It is also known that in experimental animals fed aluminum (Al), Al at micromolar level selectively accumulates in the brain, In the present study, are examined the effects of Al accumulate d in the brain cells on iron transport by the TI-IU system and iron me tabolism, using primary cultures from fetal rat cerebral cortex. Pretr eatment of cells with 200 mu M Al-nitrilotriacetate upregulated the Tf -IU system for iron. Moreover, of various metals tested, Al markedly u pregulated the TB-IU activity. To examine the influence of Al on iron metabolism, the interaction between Al accumulated in the cells and ir on-responsive element binding protein (IRE-BP), a cellular iron regula tor, was examined by Northern blot analysis, and activity assay: Al de creased the Tf receptor mRNA level and increased the aconitase activit y of IRE-BP. The increase of aconitase activity by Al was also observe d in vitro, These results suggest that Al accumulated in cortical cell s affects iron metabolism.