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首页> 外文期刊>Cell and Tissue Research >Brain region-specific vulnerability of astrocytes in response to 3-nitropropionic acid is mediated by cytochrome c oxidase isoform expression
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Brain region-specific vulnerability of astrocytes in response to 3-nitropropionic acid is mediated by cytochrome c oxidase isoform expression

机译：细胞色素C氧化酶同工型表达介导星形胶质细胞对3-硝基丙酸的脑区域特异性脆弱性

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摘要

Brain region specificity is a feature characteristic of neurodegenerative disorders, such as Huntington’s disease (HD). We have studied the brain region-specific vulnerability of striatal compared with cortical and mesencephalic astrocytes treated with 3-nitropropionic acid (NPA), an in vitro model of HD. Mitochondrial dysfunction is involved in neurodegenerative processes. We have previously demonstrated a causal relationship between NPA-induced transcription of the cytochrome c oxidase (COX) subunit IV isoform (cox4i2) and increased oxidative stress leading to higher rates of necrotic cell death in striatal astrocytes by the application of a small interfering RNA knockdown system. Here, we have investigated the correlation of COX IV-2 protein expression with intracellular ATP content, mitochondrial peroxide production, and viability of astrocytes from three different brain regions. In cortical and mesencephalic astrocytes, NPA caused an elevation of cox4i2 transcription as in striatal astroglia. However, increased COX IV-2 and decreased COX IV-1 protein expression levels have been observed only in striatal astrocytes. In agreement with our hypothesis, Striatal astrocytes showed the highest levels of peroxide production and necrotic cell death rates compared with cortical and mesencephalic astroglia. Thus, we suggest that the higher vulnerability of astrocytes from the striatum in our in vitro model of HD is, at least in part, based on brain region-specific differences of the COX IV-2/COX IV-1 protein ratios and accompanied elevated oxidative stress.
机译：大脑区域的特异性是诸如亨廷顿舞蹈病（HD）等神经退行性疾病的特征。与HD体外模型3-硝基丙酸（NPA）处理的皮层和中脑星形胶质细胞相比，我们已经研究了纹状体在大脑区域的特定脆弱性。线粒体功能障碍涉及神经退行性过程。我们以前已经证明了NPA诱导的细胞色素C氧化酶（COX）亚基IV亚型（cox4i2）的转录与氧化应激的增加之间的因果关系，这通过使用小干扰RNA敲低的应用导致纹状体星形胶质细胞坏死细胞死亡的发生率更高系统。在这里，我们研究了COX IV-2蛋白表达与细胞内ATP含量，线粒体过氧化物的产生以及来自三个不同大脑区域的星形胶质细胞活力的相关性。在皮层和中脑星形胶质细胞中，NPA导致纹状体星形胶质细胞中cox4i2转录的升高。但是，仅在纹状体星形胶质细胞中观察到了COX IV-2增加和COX IV-1蛋白表达降低。与我们的假设相符，纹状体星形胶质细胞比皮质和中脑性星形胶质细胞显示出最高水平的过氧化物生成和坏死细胞死亡率。因此，我们认为在我们的HD体外模型中，纹状体中星形胶质细胞的较高易损性至少部分是基于COX IV-2 / COX IV-1蛋白比率的脑区域特异性差异并伴有升高氧化应激。

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