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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson's disease.
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Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson's disease.

机译：铁调节基因表达的变化发生在帕金森氏病的人类细胞培养模型中。

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BACKGROUND: Neuronal iron accumulation is thought to be relevant to the pathogenesis of Parkinson's disease (PD), although the mechanism remains elusive. We hypothesized that neuronal iron uptake may be stimulated by functional mitochondrial iron deficiency. OBJECTIVE: To determine firstly whether the mitochondrial toxin, 1-methyl-4-phenylpyridinium iodide (MPP(+)), results in upregulation of iron-import proteins and transporters of iron into the mitochondria, and secondly whether similar changes in expression are induced by toxins with different mechanisms of action. METHODS: We used quantitative PCR and Western blotting to investigate expression of the iron importers, divalent metal transporter, transferrin receptor 1 and 2 (TfR1 and TfR2) and mitoferrin-2 and the iron exporter ferroportin in differentiated SH-SY5Y cells exposed to three different toxins relevant to PD, MPP(+), paraquat (a free radical generator) and lactacystin (an inhibitor of the ubiquitin-proteasome system (UPS)). RESULTS: MPP(+) resulted in increased mRNA and protein levels of genes involved in cellular iron import and transport into the mitochondria. Similar changes occurred following exposure to paraquat, another inducer of oxidative stress. Lactacystin also resulted in increased TfR1 mRNA levels, although the other changes were not found. CONCLUSION: Our results support the hypothesis of a functional mitochondrial iron deficit driving neuronal iron uptake but also suggest that differences exist in neuronal iron handling induced by different toxins.
机译：背景：尽管该机制尚不清楚，但神经元铁的积累被认为与帕金森氏病（PD）的发病机理有关。我们假设功能性线粒体铁缺乏可能刺激神经元铁的摄取。目的：首先确定线粒体毒素1-甲基-4-苯基碘化碘（MPP（+））是否导致铁输入蛋白和铁转运到线粒体中的表达上调，其次是否诱导相似的表达变化通过具有不同作用机理的毒素。方法：我们使用定量PCR和Western印迹法研究了在三种不同的分化的SH-SY5Y细胞中铁导入剂，二价金属转运蛋白，转铁蛋白受体1和2（TfR1和TfR2）以及mitoferrin-2和铁输出铁蛋白转运蛋白的表达。与PD，MPP（+），百草枯（自由基产生剂）和乳腺素（泛素-蛋白酶体系统（UPS）的抑制剂）相关的毒素。结果：MPP（+）导致参与细胞铁导入和运输到线粒体中的基因的mRNA和蛋白质水平增加。暴露于另一种氧化应激诱导剂百草枯后，发生了类似的变化。 Lactacystin还导致TfR1 mRNA水平升高，尽管未​​发现其他变化。结论：我们的结果支持功能性线粒体铁缺乏症驱动神经元铁摄取的假说，但也表明不同毒素诱导的神经元铁处理中存在差异。

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