Heterogenous distribution of ferroportin-containing neurons in mouse brain
Heterogenous distribution of ferroportin-containing neurons in mouse brain
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DOI：
10.1007/s10534-010-9405-2
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发表时间：
2011-04-01
期刊：
影响因子：
3.5
通讯作者：
Moos, Torben
中科院分区：
文献类型：
--
作者：
Boserup, Michael W.;Lichota, Jacek;Moos, Torben
铁对神经细胞中的各种细胞功能至关重要。神经元的铁摄取反映在转铁蛋白受体和二价金属转运蛋白1(DMT 1)的强健和一致表达上。相反，神经元中和并可能排泄铁的机制不太清楚。研究表明，神经元表达铁蛋白，这可能反映了一种铁输出机制。我们用一种抗体绘制了成年小鼠脑内铁蛋白的分布，该抗体由代表小鼠铁蛋白的223-303氨基酸序列的多肽制备而成。该抗体在脑匀浆中特异性地检测到铁蛋白，而培养的内皮细胞匀浆中则没有免疫反应性。在脑切片中，铁蛋白主要分布于大脑皮层、海马、丘脑、脑干和小脑的神经元胞体和外周突起。在脑干，脑神经核团和网状结构的神经元中铁-孔蛋白的标记程度尤其高。在纹状体、苍白球或下丘脑中几乎检测不到铁蛋白。在非神经细胞中，少突胶质细胞和脉络丛上皮细胞中可检测到铁蛋白。与以往对转铁蛋白受体在神经元中分布的研究相比，许多神经元池与那些表达铁蛋白的神经元池相吻合。因此，数据表明，神经元铁稳态由转铁蛋白受体介导的铁转铁蛋白摄取和铁转铁蛋白相关的铁排泄之间的微妙平衡组成。这些发现还表明，在缰核、海马体、网状结构和小脑等神经元区域，铁的周转特别高，因为这些区域的几个神经元显示出转铁蛋白受体和铁蛋白的显著共表达。
Iron is crucial for a variety of cellular functions in neuronal cells. Neuronal iron uptake is reflected in a robust and consistent expression of transferrin receptors and divalent metal transporter 1 (DMT 1). Conversely, the mechanisms by which neurons neutralize and possibly excrete iron are less clear. Studies indicate that neurons express ferroportin which could reflect a mechanism for iron export. We mapped the distribution of ferroportin in the adult mouse brain using an antibody prepared from a peptide representing amino acid sequences 223-303 of mouse ferroportin. The antibody specifically detected ferroportin in brain homogenates, whereas homogenates of cultured endothelial cells were devoid of immunoreactivity. In brain sections, ferroportin was confined to neuronal cell bodies and peripheral processes of cerebral cortex, hippocampus, thalamus, brain stem, and cerebellum. In brain stem ferroportin-labeling was particularly high in neurons of cranial nerve nuclei and reticular formation. Ferroportin was hardly detectable in striatum, pallidum, or hypothalamus. Among non-neuronal cells, ferroportin was detected in oligodendrocytes and choroid plexus epithelial cells. A comparison with previous studies on the distribution of transferrin receptors in neurons shows that many neuronal pools coincide with those expressing ferroportin. The data therefore indicate that neuronal iron homeostasis consists of a delicate balance between transferrin receptor-mediated uptake of iron-transferrin and ferroportin-related iron excretion. The findings also suggest a particular high turnover of iron in neuronal regions, such as habenula, hippocampus, reticular formation and cerebellum, as several neurons in these regions exhibit a prominent co-expression of transferrin receptors and ferroportin.