...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Evidence that mouse brain neuropathy target esterase is a lysophospholipase
【24h】

Evidence that mouse brain neuropathy target esterase is a lysophospholipase

机译：小鼠脑神经病目标酯酶是溶血磷脂酶的证据

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

Neuropathy target esterase (NTE) is inhibited by several organophosphorus (OP) pesticides, chemical warfare agents, lubricants, and plasticizers, leading to OP-induced delayed neuropathy in people (>30,000 cases of human paralysis) and hens (the best animal model for this demyelinating disease). The active site region of NTE as a recombinant protein preferentially hydrolyzes lysolecithin, suggesting that this enzyme may be a type of lysophospholipase (LysoPLA) with lysolecithin as its physiological substrate. This hypothesis is tested here in mouse brain by replacing the phenyl valerate substrate of the standard NTE assay with lysolecithin for an "NTE-LysoPLA" assay with four important findings. First, NTE-LysoPLA activity, as the NTE activity, is 41-45% lower in Nte-haploinsufficient transgenic mice than in their wild-type littermates. Second, the potency of six delayed neurotoxicants or toxicants as in vitro inhibitors varies from IC50 0.02 to 13,000 nM and is essentially the same for NTE-LysoPLA and NTE (r(2) = 0.98). Third, the same six delayed toxicants administered i.p. to mice at multiple doses inhibit brain NTE-LysoPLA and NTE to the same extent (r(2) = 0.90). Finally, their in vivo inhibition of brain NTE-LysoPLA generally correlates with delayed toxicity. Therefore, OP-induced delayed toxicity in mice, and possibly the hyperactivity associated with NTE deficiency, may be due to NTE-LysoPLA inhibition, leading to localized accumulation of lysolecithin, a known demyelinating agent and receptor-mediated signal transducer. This mouse model has some features in common with OP-induced delayed neuropathy in hens and people but differs in the neuropathological signs and apparently the requirement for NTE aging. [References: 48]
机译：神经病靶标酯酶（NTE）被多种有机磷（OP）农药，化学战剂，润滑剂和增塑剂抑制，导致人（> 30,000例瘫痪）和母鸡（对于动物而言，最佳动物模型）导致OP引起的延迟性神经病。这种脱髓鞘疾病）。作为重组蛋白的NTE的活性位点区域优先水解溶血卵磷脂，表明该酶可能是以溶血卵磷脂为生理底物的溶血磷脂酶（LysoPLA）。在此通过在鼠脑中测试此假设，方法是用溶血卵磷脂取代标准NTE分析的戊酸苯基底物，用于“ NTE-LysoPLA”分析，有四个重要发现。首先，在Nte-单倍体不足的转基因小鼠中，NTE-LysoPLA活性（作为NTE活性）比其野生型同窝小鼠低41-45％。其次，作为体外抑制剂的六种延迟神经毒物或毒物的效力从IC50 0.02到13,000 nM不等，对于NTE-LysoPLA和NTE基本相同（r（2）= 0.98）。第三，经腹膜内注射同样的六种延迟毒药。对小鼠以多次剂量抑制脑NTE-LysoPLA和NTE的程度相同（r（2）= 0.90）。最后，它们在体内对脑NTE-LysoPLA的抑制作用通常与延迟毒性有关。因此，OP诱导的小鼠延迟毒性，以及可能与NTE缺乏相关的过度活跃，可能是由于NTE-LysoPLA抑制所致，导致溶血卵磷脂（一种已知的脱髓鞘剂和受体介导的信号转导物）的局部积累。该小鼠模型与母鸡和人的OP引起的迟发性神经病具有某些共同特征，但是神经病理学标志不同，并且显然需要NTE衰老。 [参考：48]

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