Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron.
Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron.
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DOI：
10.1016/j.taap.2008.02.024
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发表时间：
2008-07
影响因子：
3.8
通讯作者：
Xueqian Wang;David S. Miller;Wei Zheng
中科院分区：
文献类型：
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作者：
Xueqian Wang;David S. Miller;Wei Zheng
共聚焦显微镜用于研究锰（Mn）和铁（Fe）暴露对金属转运蛋白亚细胞分布的影响，即，二价金属转运蛋白1（DMT 1）、金属转运蛋白1（MTP 1）和转铁蛋白受体（TfR）在大鼠完整脉络丛中的表达。在对照组织中，DMT 1集中在顶端上皮膜下方，MTP 1弥漫在细胞质内，TfR分布在细胞核周围的囊泡中。Mn或Fe处理（1和10 μM）后，DMT 1的分布不受影响。然而，MTP 1和TfR明显向细胞的顶极移动。当微管被破坏时，这些变化被取消。定量RT-PCR和Western blot分析显示，锰暴露后，TfR的mRNA和蛋白水平显着增加，但不是DMT 1和MTP 1。这些结果表明，在组织响应锰或铁暴露的早期事件涉及微管依赖性，细胞内的MTP 1和TfR的贩运。锰暴露后脉络丛中金属转运蛋白的细胞内运输可能部分导致锰暴露后脑脊液（CSF）中Fe稳态的锰诱导破坏。
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 μM), 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.