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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 >Brain region specificity of 3-nitropropionic acid-induced vulnerability of neurons involves cytochrome c oxidase.
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Brain region specificity of 3-nitropropionic acid-induced vulnerability of neurons involves cytochrome c oxidase.

机译：3-硝基丙酸诱导的神经元脆弱性的脑区域特异性涉及细胞色素c氧化酶。

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摘要

Mitochondria play a pivotal role in the regulation of energy metabolism and apoptotic pathways. Properties and functions of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to a different extent to cellular stress and degeneration. We have investigated the effect of 3-nitropropionic acid (NPA), a mitochondrial toxin and mimicking symptoms of Huntington's disease (HD) when applied systemically, on mitochondrial function and viability of primary neurons isolated from mouse brain striatum and cortex. We observed a higher vulnerability of striatal compared with cortical neurons in response to NPA treatment. This effect might be correlated with the transcription pattern of cytochrome c oxidase (EC 1.9.3.1.; COX) subunit IV isoforms. In cortical neurons, NPA induced a down-regulation of the COX IV-2/COX IV-1 ratio, whereas an up-regulation was found in striatal neurons. Previously, we have shown that an increased COX IV-2/COX IV-1 ratio is responsible for a higher enzyme activity which is paralleled by elevated intracellular ATP levels at the expense of increased mitochondrial peroxide production. These effects could also be demonstrated in striatal neurons. On the contrary, a decreased COX IV-2/COX IV-1 ratio was observed in cortical neurons which was accompanied by a decrease in intracellular ATP content and no significant changes in mitochondrial peroxide production. We propose that COX isoform IV-2 mediates increased oxidative stress that is, at least in part, responsible for a higher vulnerability of striatal compared with cortical neurons against NPA. This mechanism, in turn, may serve as an explanation for brain region-specific differences in the neuronal susceptibility to toxic conditions.
机译：线粒体在能量代谢和凋亡途径的调节中起关键作用。线粒体的特性和功能可能使选择性易受攻击的神经元的子集固有地对细胞应激和变性程度不同。我们已经研究了3-硝基丙酸（NPA），线粒体毒素和系统应用亨廷顿舞蹈病（HD）的模仿症状对线粒体功能和从小鼠脑纹状体和皮层分离的初级神经元活力的影响。我们观察到，对NPA治疗的反应，纹状体的脆弱性高于皮质神经元。这种作用可能与细胞色素c氧化酶（EC 1.9.3.1 .; COX）亚基IV亚型的转录模式有关。在皮层神经元中，NPA诱导了COX IV-2 / COX IV-1比值的下调，而在纹状体神经元中却发现了上调。以前，我们已经表明，增加的COX IV-2 / COX IV-1比率负责较高的酶活性，这与增加的细胞内ATP水平相对应，但以增加的线粒体过氧化物产生为代价。这些效应也可以在纹状体神经元中证明。相反，在皮层神经元中观察到COX IV-2 / COX IV-1比例降低，这伴随着细胞内ATP含量的降低，线粒体过氧化物的产生没有明显变化。我们建议，COX亚型IV-2介导增加的氧化应激，这至少部分是导致纹状体比NPA皮质神经元更高的脆弱性的原因。反过来，该机制可以解释神经元对毒性条件的敏感性中脑区域特定差异。

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