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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Glial cells contribute more to iron and aluminum accumulation but are more resistant to oxidative stress than neuronal cells
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Glial cells contribute more to iron and aluminum accumulation but are more resistant to oxidative stress than neuronal cells

机译：胶质细胞比神经元细胞对铁和铝的积累贡献更大，但对氧化应激的抵抗力更强

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摘要

Iron (Fe) and aluminum (Al) have been implicated in the pathogenesis of Alzheimer's disease (AD). In this study, we examined neuronal and glial cells to clarify which contributes most to metal accumulation after internalization through the transferrin-independent iron uptake (Tf-IU) systems in primary neuronal and glial predominant (NP and GP) cells from rat cerebral cortex, which affect the accumulation of transition metals in a variety of cultured cells. Al more significantly upregulated the Tf-IU activity in GP cells than in NP cells. GP cells were more resistant to Fe and Al exposure than NP cells. However, a chemiluminescence analysis specific for reactive oxygen species (ROS) showed that ROS levels in Fe- or Al-loaded NP cells were twice as high as in Fe- or Al-loaded GP cells. Northern blot analysis and gel retardation assay showed that the Al and Fe exposure taken up by the cells suppress Tf receptor mRNA expression to a greater extent in GP than NP cells, indicating that Al and Fe more markedly accumulate in glial than in neuronal cells. These results suggest that glial cells rather than neuronal cells contribute to the metal accumulation and are more resistant to oxidative stress caused by metals than neuronal cells. the present study may help to explain the pathogenesis of neurodegeneration in AD disorders caused by metal-generated oxidative stress.
机译：铁（Fe）和铝（Al）与阿尔茨海默氏病（AD）的发病机理有关。在这项研究中，我们检查了神经元和神经胶质细胞，以阐明在通过大鼠脑皮层的原代神经元和神经胶质优势（NP和GP）细胞中，通过转铁蛋白独立的铁吸收（Tf-IU）系统内化后，对金属积累的贡献最大。会影响各种培养细胞中过渡金属的积累。与NP细胞相比，A1在GP细胞中更显着上调了Tf-IU活性。 GP细胞比NP细胞更耐Fe和Al暴露。但是，针对活性氧（ROS）的化学发光分析表明，铁或铝负载NP细胞中的ROS水平是铁或铝负载GP细胞中ROS的两倍。 Northern印迹分析和凝胶阻滞分析显示，细胞摄取的Al和Fe暴露比NP细胞更大程度地抑制GP中Tf受体mRNA的表达，表明Al和Fe比神经元细胞更明显地聚集在神经胶质中。这些结果表明，与神经元细胞相比，神经胶质细胞而不是神经元细胞促进了金属的积累，并且更能抵抗金属引起的氧化应激。本研究可能有助于解释由金属产生的氧化应激引起的AD疾病中神经退行性病变的发病机理。

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