Abnormal development and increased 3-nitrotyrosine in copper-deficient mouse embryos
Abnormal development and increased 3-nitrotyrosine in copper-deficient mouse embryos
复制标题
DOI：
10.1016/j.freeradbiomed.2005.08.020
复制
发表时间：
2006-01-01
影响因子：
7.4
通讯作者：
Uriu-Adams, JY
中科院分区：
文献类型：
--
作者：
Beckers-Trapp, ME;Lanoue, L;Uriu-Adams, JY
铜缺乏大鼠胚胎的特征是大脑和心脏异常，超氧化物歧化酶活性低，超氧阴离子浓度高。超氧阴离子增加的一个后果是形成过氧亚硝酸盐，这是一种强烈的生物氧化剂。为了研究铜缺乏的重要发育特征，将来自铜充足和铜缺乏的GD8.5小鼠胚胎分别培养在铜充足和铜缺乏的培养液中。48小时后，缺铜胚胎表现出脑和心脏异常，卵黄囊血管异常的发生率高于对照组。4-羟基-2‘-脱氧鸟苷和4-羟基-2’-脱氧鸟苷对脂质和DNA损伤的免疫组织化学在组间相似。相反，作为蛋白质硝化指标的3-硝基酪氨酸在铜缺乏胚胎的前神经管神经上皮细胞中显著高于对照组。补充铜或补充铜锌超氧化物歧化酶、TIron或谷胱甘肽过氧化物酶均不能改善低铜胚胎神经上皮细胞的异常发育，但可降低3-硝基酪氨酸的含量。这些数据支持这样的观点，即虽然铜缺乏损害了氧化防御并增加了蛋白质的硝化作用，但其他机制，如一氧化氮代谢的改变，可能有助于铜缺乏诱导的畸形发生。(C)2005 Elsevier Inc.保留所有权利。
Copper-deficient rat embryos are characterized by brain and heart anomalies, low superoxide dismutase activity, and high superoxide anion concentrations. One consequence of increased superoxide anions can be the formation of peroxynitrite, a strong biological oxidant. To investigate developmentally important features of copper deficiency, GD 8.5 mouse embryos from copper-adequate and copper-deficient dams were cultured in media that were adequate or deficient in copper. After 48 h, copper-deficient embryos exhibited brain and heart anomalies, and a high incidence of yolk sac vasculature abnormalities compared to controls. Immunohistochemistry of 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine for lipid and DNA damage, respectively, was similar between groups. In contrast, 3-nitrotyrosine, taken as a measure of protein nitration, was markedly higher in the neuroepithelium of the anterior neural tube of copper-deficient embryos than in controls. Repletion of copper-deficient media with copper, or supplementation with copper-zinc superoxide dismutase, Tiron, or glutathione peroxidase did not ameliorate the abnormal development, but did decrease 3-nitrotyrosine in neuroepithelium of copper-deficient embryos. These data support the concept that while copper deficiency compromises oxidant defense and increases protein nitration, additional mechanisms, e.g., altered nitric oxide metabolism may contribute to copper-deficiency-induced teratogenesis. (c) 2005 Elsevier Inc. All rights reserved.