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首页> 外文期刊>Scientific reports. >Multi-copper ferroxidase deficiency leads to iron accumulation and oxidative damage in astrocytes and oligodendrocytes
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Multi-copper ferroxidase deficiency leads to iron accumulation and oxidative damage in astrocytes and oligodendrocytes

机译：多铜铁杂种酶缺乏导致星形胶质细胞和少突胶质细胞的铁积累和氧化损伤

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Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin (Heph) and ceruloplasmin (Cp) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph, Cp, and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.
机译：铁的积累已经与中枢神经系统的各种疾病的病理学相关。我们以前的作品表明，Hephaestin（Heph）和帽子（CP）双敲除（KO）小鼠诱导多脑区域的铁积累，这通过增加的氧化损伤和认知记忆缺陷并平行。在这项研究中，我们从新生儿野生型（WT），Heph Ko和Cp Ko小鼠的脑皮质中富集了星形细胞和少突胚细胞。我们证明Heph在少突胶质细胞中高度表达，而CP主要表达于星形胶质细胞中。在CP KO星形胶质细胞和Heph Ko oligeDendrocytes中损害铁流出，并且与氧化胁迫增加有关。 Heph，Cp和其他铁相关基因的表达在星形胶质细胞和oligodendrocytes中检查，无论是否有铁处理。有趣的是，我们发现编码脱盐素1的mRNA的表达，与CP和HEPH与细胞出口铁的跨膜蛋白与星形胶质细胞中的CP表达呈正相关，并且在少突胶中的Heph表达。我们的调查结果集体证明Heph和CP对防止胶质粘度很重要，因此可能对氧化损伤进行保护。

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