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PMID:18420243

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Citation

Wang, X, Miller, DS and Zheng, W (2008) Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron. Toxicol. Appl. Pharmacol. 230:167-74

Abstract

Confocal microscopy was used to investigate the effects of manganese (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 comprises the blood-cerebrospinal fluid barrier. In 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 treatment (1 and 10 microM), the distribution of DMT1 was not affected. However, MTP1 and TfR moved markedly toward the apical pole of the cells. These shifts were abolished 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 early events in the tissue response to Mn or Fe exposure involve microtubule-dependent, intracellular trafficking of MTP1 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.

Links

PubMed PMC2586425 Online version:10.1016/j.taap.2008.02.024

Keywords

Animals; Antineoplastic Agents/pharmacology; Blotting, Western; Cation Transport Proteins/metabolism; Choroid Plexus/drug effects; Choroid Plexus/metabolism; Choroid Plexus/ultrastructure; Cytochalasin D/pharmacology; Immunohistochemistry; Iron/pharmacology; Male; Manganese/pharmacology; Metals/metabolism; Microscopy, Confocal; Microscopy, Fluorescence; Nocodazole/pharmacology; Nucleic Acid Synthesis Inhibitors/pharmacology; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Rats; Rats, Sprague-Dawley; Receptors, Transferrin/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Subcellular Fractions/drug effects; Subcellular Fractions/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:NRAM2

located_in

GO:0045177: apical part of cell

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:NRAM2

part_of

GO:0045177: apical part of cell

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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