Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron

Confocal microscopy was used to investigate the effects of manganses(Mn) and iron(Fe) exposure on the subcellular distribution of metal transporting proteins, i.e., divalent metal transporter 1(DMT1), metal transporter protein 1(MTP1), and transferrin receptor(TfR), in the rat intact choroid plexus which comprise the blood-cerebrospinal fluid barrier. In control tiIn control tissue, DMT1 was concentrated below the apical epithelial membrane, MTP1 was diffuse within the cytosol, and TfR was distributed in vesicles around nuclei. Following Mn or Fe treatement (1 and 10 mu M), the distribution of DMT1 was not affected when microtubules were disrupted. Quantitative RT-PCR and Western blot analyses revealed a significant increase in mRNA and protein levels of TfR but not DMT1 and MTP1 after Mn exposure. These results suggest that earlyevents in the tissue response to Mn or Fe exposure involve microtubule-dependent, intracellular trafficking ofMTP1 and TfR.The intracellular trafficking of metal transporters in the choroid plexus following Mn exposure may partially contribute to Mn-induced disruption in Fe homeostasis in the cerebrospinal fluid (CSF) following Mn exposure.(c) 2008 Elsevier Inc. All rights reserved.