Characterization of a transferrin-independent iron uptake system in rat primary cultured cortical cells

Multiple transferrin-independent iron uptake (Tf-IU) systems are known to be involved in the internalization of free iron salt in various mammalian cells. However, the characteristics of a Tf-IU system in cortical cells are not clear. In this study, we characterized the Tf-IU systems in both cortical and glial predominant (GP) cells from rat cerebral cortex to investigate the mechanism by which iron (Fe) or aluminum (Al) accumulates in the cerebral cortex. The Tf-IU systems in both cells were temperature- and Ca2*-dependent. The upregulation of Tf-IU system in GP cells by Fe- or Al-nitrilotriacetate (Fe- or AI-NTA) was 2- or 4-fold higher than that of cortical cells. Chemiluminescence analysis specific for O2- and 1O2 also showed that the production of active oxygen species in Fe-loading GP cells was twice higher than that of Fe-loading cortical cells. These results suggest the existence of Tf-IU systems in both cortical and GP cells similar to those of HeLa cells whose Tf-IU is metal- and Ca-2+ dependent, and that the glial cells contribute to metal accumulation in cerebral cortex. The present study may help to explain the pathogenesis of neurodegenerative disorders caused by inducing oxidative stress.