The neuroprotectant ebselen inhibits oxidative DNA damage induced by dopamine in the presence of copper ions.
The neuroprotectant ebselen inhibits oxidative DNA damage induced by dopamine in the presence of copper ions.
复制标题
神经保护剂依布硒啉可抑制多巴胺在铜离子存在下诱导的氧化性 DNA 损伤。
DOI：
10.1016/s0304-3940(02)00444-5
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发表时间：
2002
影响因子：
2.5
通讯作者：
Cao,Zhuoxiao
中科院分区：
文献类型：
--
作者：
Li,Yunbo;Cao,Zhuoxiao
Ebselen (2-苯基-1,2-苯并异硒唑-3(2H)-one) 是一种具有谷胱甘肽过氧化物酶样活性的硒代有机化合物，已被证明可以预防脑缺血性损伤和帕金森病。本研究旨在探讨依布硒啉 (ebselen) 对铜离子存在下多巴胺诱导的氧化 DNA 损伤的保护作用。在 Cu(II) 存在下，将 φX-174 质粒 DNA 与微摩尔多巴胺一起孵育，会导致浓度依赖性的 DNA 链断裂诱导。 Cu(II)/Cu(I) 氧化还原循环和 H2O2 形成都与多巴胺/Cu(II) 系统诱导 DNA 链断裂密切相关。微摩尔浓度的依布硒啉对多巴胺/Cu(II)系统诱导的DNA链断裂产生显着的浓度依赖性抑制。进一步的研究表明，依布硒啉既不影响 Cu(II) 介导的多巴胺氧化为多巴胺醌，也不影响多巴胺将 Cu(II) 还原为 Cu(I)。相反，依布硒啉的存在导致由 Cu(II) 介导的多巴胺氧化产生的 H2O2 水平显着降低。综上所述，我们的结果首次证明依布硒啉能够抑制多巴胺/Cu(II)诱导的氧化性DNA损伤，这似乎归因于依布硒啉能够降低来自多巴胺/Cu(II)系统的H2O2水平。由于氧化性 DNA 损伤与各种神经退行性疾病的发病机制有关，依布硒啉对氧化性 DNA 损伤的抑制可能是（至少部分）其在人类和实验动物中观察到的神经保护活性的原因。
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a seleno-organic compound with glutathione peroxidase-like activity, has been shown to be protective against brain ischemic injury and Parkinson's disease. This study was undertaken to investigate the protective effects of ebselen on oxidative DNA damage induced by dopamine in the presence of copper ions. Incubation of φX-174 plasmid DNA with micromolar dopamine in the presence of Cu(II) resulted in a concentration-dependent induction of DNA strand breaks. Both a Cu(II)/Cu(I) redox cycle and H2O2formation were critically involved in the induction of DNA strand breaks by the dopamine/Cu(II) system. The presence of ebselen at micromolar concentrations led to a marked concentration-dependent inhibition of DNA strand breaks induced by the dopamine/Cu(II) system. Further studies showed that ebselen did not affect either the Cu(II)-mediated oxidation of dopamine to dopamine quinone or the reduction of Cu(II) to Cu(I) by dopamine. Instead, the presence of ebselen resulted in a marked decrease in the levels of H2O2derived from the Cu(II)-mediated oxidation of dopamine. Taken together, our results demonstrate for the first time that ebselen is able to inhibit the dopamine/Cu(II)-induced oxidative DNA damage, which appears to be attributable to the ability of ebselen to decrease the levels of H2O2derived from the dopamine/Cu(II) system. Since oxidative DNA damage has been implicated in the pathogenesis of various neurodegenerative diseases, the inhibition of oxidative DNA damage by ebselen may be responsible, at least partially, for its neuroprotective activities observed in both humans and experimental animals.