Myricetin affords protection against peroxynitrite-mediated DNA damage and hydroxyl radical formation
Myricetin affords protection against peroxynitrite-mediated DNA damage and hydroxyl radical formation
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杨梅素可防止过氧亚硝酸盐介导的 DNA 损伤和羟基自由基的形成
DOI：
10.1016/j.fct.2011.06.066
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发表时间：
2011-09-01
影响因子：
4.3
通讯作者：
Li, Ang
中科院分区：
文献类型：
--
作者：
Chen, Wei;Li, Yudong;Li, Ang
过氧亚硝酸盐通过其细胞毒性作用广泛参与各种形式的神经退行性疾病的发病机制，本研究旨在研究杨梅素的神经保护作用是否与抑制过氧亚硝酸盐介导的DNA损伤有关，这是导致过氧亚硝酸盐引起细胞毒性的关键事件。我们观察到过氧亚硝基阴离子可引起phi X-174质粒DNA和大鼠原代星形胶质细胞DNA损伤。发现生理浓度的杨梅素的存在显著抑制由过氧亚硝基阴离子及其产生剂3-吗啉代壬亚胺（SIN-1）诱导的DNA链断裂。此外，SIN-1引起的氧消耗被发现在杨梅素的存在下降低，表明杨梅素可能影响SIN-1的自氧化。此外，EPR光谱表明，形成DMPO-羟基自由基加合物（DMPO-OH）从过氧亚硝酸盐，和杨梅苷抑制加合物的信号在浓度依赖性的方式。综上所述，这些结果首次表明，杨梅素可以抑制过氧亚硝酸盐介导的DNA损伤和羟基自由基的形成。(C)2011爱思唯尔有限公司保留所有权利。
Peroxynitrite has been extensively implicated in the pathogenesis of various forms of neurodegenerative disorders via its cytotoxic effects, this study was undertaken to investigate whether the neuroprotective effect of myricetin is associated with inhibition of peroxynitrite-mediated DNA damage, a critical event leading to peroxynitrite elicited cytotoxicity. We observed that peroxynitrite can cause DNA damage in phi X-174 plasmid DNA and rat primary astrocytes. The presence of myricetin at physiological concentration was found to significantly inhibit DNA strand breakage induced by both peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1). Moreover, the consumption of oxygen caused by SIN-1 was found to be decreased in the presence of myricetin, indicating that myricetin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy demonstrated that the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from peroxynitrite, and that myricetin inhibited the adduct signal in a concentration-dependent manner. Taken together, these results demonstrate for the first time that myricetin can inhibit peroxynitrite-mediated DNA damage and hydroxyl radical formation. (C) 2011 Elsevier Ltd. All rights reserved.