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J. Biochem, 1998, Vol. 123, No. 1 42-46
© 1998 Japanese Biochemical Society

research-article

Aluminum Taken Up by Transferrin-Independent Iron Uptake Affects the Iron Metabolism in Rat Cortical Cells

Satoru Oshiro*,1, Masahiro Kawahara{dagger}, Shirao Mika§, Kazuyo Muramoto{dagger}, Kazuo Kobayashi{dagger}, Ryuta Ishige{ddagger}, Koji Nozawa{ddagger}, Makoto Hori{ddagger}, Cai Yungd, Shigetaka Kitajima* and Yoichiro Kuroda{dagger}

*Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034
{dagger}Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neurosciences Fuchu, Tokyo 183
{ddagger}Department of Biochemistry, Showa Pharmaceutical Sciences 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194
§Institute of Public Health, Department of Pharmacology 4-6-1 Shiroganedai, Minato-ku, Tokyo 108
dDepartment of Clinical Chemistry and Laboratory Medicine, Kyusyu University Fukuoka 812-82

1To whom correspondence should be addressed. E-mail: Satoru.bgen{at}mri.tmd.ac.jp

We previously demonstrated that cultured human fibroblasts internalize iron via transferrin-independent iron uptake (Tf-IU), redox, and receptor-mediated endocytosis uptake systems [Oshiro, S., Nakajima, H., Markello, T., Krasnewich, D., Bernardini, I., and Gahl, W.A. (1993) J. Biol. Chem. 268, 21586–21591]. Of these iron transport systems, the Tf-IU system is involved in the accumulation of transition metals in various 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, we examined the effects of Al accumulated in the brain cells on iron transport by the Tf-IU system and iron metabolism, using primary cultures from fetal rat cerebral cortex. Pretreatment of cells with 200 µM Al-nitrilotriacetate upregulated the Tf-IU system for iron. Moreover, of various metals tested, Al markedly upregulated the Tf-IU activity. To examine the influence of Al on iron metabolism, the interaction between Al accumulated in the cells and iron-responsive element binding protein (IRE-BP), a cellular iron regulator, was examined by Northern blot analysis, and activity assay: Al decreased the Tf receptor mRNA level and increased the aconitase activity of IRE-BP. The increase of aconitase activity by Al was also observed in vitro. These results suggest that Al accumulated in cortical cells affects iron metabolism.


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