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首页> 外文期刊>Biochemistry >Cuprizone Intoxication Induces Cell Intrinsic Alterations in Oligodendrocyte Metabolism Independent of Copper Chelation
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Cuprizone Intoxication Induces Cell Intrinsic Alterations in Oligodendrocyte Metabolism Independent of Copper Chelation

机译：铜沸腾中毒诱导寡突胶质细胞代谢中的细胞内在改变，与铜螯合无关

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Cuprizone intoxication is a common animal model used to test myelin regenerative therapies for the treatment of diseases such as multiple sclerosis. Mice fed this copper chelator develop reversible, region-specific oligodendrocyte loss and demyelination. While the cellular changes influencing the demyelinating process have been explored in this model, there is no consensus about the biochemical mechanisms of toxicity in oligodendrocytes and about whether this damage arises from the chelation of copper in vivo. Here we have identified an oligodendroglial cell line that displays sensitivity to cuprizone toxicity and performed global metabolomic profiling to determine biochemical pathways altered by this treatment. We link these changes with alterations in brain metabolism in mice fed cuprizone for 2 and 6 weeks. We find that cuprizone induces widespread changes in one-carbon and amino acid metabolism as well as alterations in small molecules that are important for energy generation. We used mass spectrometry to examine chemical interactions that are important for copper chelation and toxicity. Our results indicate that cuprizone induces global perturbations in cellular metabolism that may be independent of its copper chelating ability and potentially related to its interactions with pyridoxal 5-phosphate, a coenzyme essential for amino acid metabolism.
机译：黄金毒性中毒是用于测试髓鞘再生疗法的常见动物模型，用于治疗多发性硬化等疾病。喂养这种铜螯合剂的小鼠显影可逆，区域特异性的少突卵细胞损失和脱髓鞘。虽然在该模型中探讨了影响脱髓苷酸化过程的细胞变化，但对少突胶质细胞中毒性的生化机制以及关于这种损伤是否出现在体内铜的螯合作用的共识。在这里，我们已经鉴定了寡突细胞细胞系，显示对铜酮毒性的敏感性，并进行全球性代谢分析以确定通过该处理改变的生物化学途径。我们将这些变化与饲喂铜苏酮的小鼠脑新陈代谢的改变联系起来2和6周。我们发现铜苏酮在一碳和氨基酸代谢中的广泛变化以及对能量产生很重要的小分子中的改变。我们使用质谱法检查对铜螯合和毒性重要的化学相互作用。我们的研究结果表明，富葡萄酒诱导细胞代谢中的全球扰动，其可能与其铜螯合能力无关，并且可能与其与吡哆醛5-磷酸盐的相互作用有关，这是氨基酸代谢的辅酶。

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