...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of biochemical and molecular toxicology >Cyanide interaction with redox modulatory sites enhances NMDA receptor responses.
【24h】

Cyanide interaction with redox modulatory sites enhances NMDA receptor responses.

机译：氰化物与氧化还原调节位点的相互作用增强了NMDA受体反应。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Activation of NMDA receptors plays an important role in cyanide neurotoxicity. Cyanide indirectly activates the receptor by inducing neuronal release of glutamate and also enhances receptor-mediated responses by a direct interaction with the receptor complex. This study investigated the mechanism in cerebellar granule cells by which cyanide enhances NMDA-induced Ca2+ influx. Cyanide (50 microM) increased the influx of Ca2+ over the NMDA concentration range of 0.5-500 microM. Experiments showed that cyanide does not interact with the receptor's glycine or PKC mediated phosphorylation regulatory sites. N-ethylmaleimide, a thiol alkylating agent which inactivates the redox regulatory sites of the receptor, blocked the enhancing effect of cyanide. Pretreatment of cells with 5,5-dithio-bis-2-nitrobenzoic acid (DTNB), a compound that oxidizes the receptor redox sites, had no effect on the response to cyanide. On the other hand, the nonpermeant reducing agents, dithiothreitol or cysteine, further increased the cyanide effect. These observations can be explained by cyanide interacting with redox sensitive disulfide groups that are not accessible to the non-permeant reducing agents. It is proposed that cyanide interacts with a redox site(s) located either on the intracellular receptor domain or in the transmembrane hydrophobic domain. Furthermore the enhancement by cyanide of the excitotoxic actions of NMDA involves receptor sites that are sensitive to oxidation/reduction and this interaction contributes to the neurotoxic action of cyanide.
机译：NMDA受体的激活在氰化物神经毒性中起重要作用。氰化物通过诱导谷氨酸的神经元释放而间接激活受体，并通过与受体复合物的直接相互作用增强受体介导的反应。这项研究调查了小脑颗粒细胞中氰化物增强NMDA诱导的Ca2 +内流的机制。氰化物（50 microM）在0.5-500 microM的NMDA浓度范围内增加了Ca2 +的流入量。实验表明，氰化物不会与受体的甘氨酸或PKC介导的磷酸化调节位点相互作用。 N-乙基马来酰亚胺是一种硫醇烷基化剂，可以使受体的氧化还原调节位点失活，从而阻止了氰化物的增强作用。用5,5-二硫代双-2-硝基苯甲酸（DTNB）（一种氧化受体氧化还原位点的化合物）对细胞进行预处理，对氰化物的反应没有影响。另一方面，不渗透还原剂二硫苏糖醇或半胱氨酸进一步提高了氰化物的作用。这些观察结果可以通过氰化物与氧化还原敏感的二硫化物基团相互作用来解释，这是非渗透还原剂无法达到的。提出氰化物与位于细胞内受体结构域或跨膜疏水结构域的氧化还原位点相互作用。此外，通过氰化物增强NMDA的兴奋性毒性作用涉及对氧化/还原敏感的受体部位，并且这种相互作用有助于氰化物的神经毒性作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号