• 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 >Myeloperoxidase up-regulates the catalytic activity of inducible nitric oxide synthase by preventing nitric oxide feedback inhibition
【24h】

Myeloperoxidase up-regulates the catalytic activity of inducible nitric oxide synthase by preventing nitric oxide feedback inhibition

机译：髓过氧化物酶通过防止一氧化氮反馈抑制而上调诱导型一氧化氮合酶的催化活性

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

Kinetic and structure analysis of inducible nitric oxide synthase (iNOS) revealed that, in addition to the increase of iNOS expression in inflamed areas, the major pathway causing overproduction of NO is destabilization of the iNOS-nitrosyl complex(es) that form during steady-state catalysis. Formation of such a complex allows iNOS to operate at only a fraction (20-30%) of its maximum activity. Thus, bioavailability of NO scavengers at sites of inflammation may play an essential role in up-regulation of the catalytic activity of iNOS, by preventing the catalytic activity inhibition that is attributed to nitrosyl complex formation. Myeloperoxidase (MPO), a major NO scavenger, is a pivotal enzyme involved in leukocyte-mediated host defenses. It is thought to play a pathogenic role under circumstances such as acute inflammatory tissue injury and chronic inflammatory conditions. However, a detailed understanding of the interrelationship between iNOS and MPO at sites of inflammation is lacking. We used direct spectroscopic, HPLC, and selective NO-electrode measurements to determine the interdependent relationship that exists between iNOS and MPO and the role of the MPO/H_2O_2 system in up-regulating the catalytic activity of iNOS that occurs at sites of inflammation. Scavenging free NO from the iNOS milieu by the MPO/H_2O_2 system subsequently restores the full capacity of iNOS to convert L-aginine to product (NO), as judged by the increase in the rates of citrulline and nitriteitrate production. Studies of iNOS catalytic mechanisms and function are essential to a more fundamental understanding of these factors, which govern iNOS-dependent processes in human health and disease.
机译：诱导型一氧化氮合酶（iNOS）的动力学和结构分析表明，除了发炎区域iNOS表达的增加外，引起NO过量产生的主要途径是iNOS-亚硝酰基复合物在稳定状态下形成的不稳定。状态催化。这种复合物的形成使iNOS只能以其最大活性的一小部分（20-30％）运行。因此，通过清除归因于亚硝酰基复合物形成的催化活性抑制，炎症清除部位的NO清除剂的生物利用度可能在iNOS催化活性的上调中起重要作用。髓过氧化物酶（MPO）是一种主要的NO清除剂，是参与白细胞介导的宿主防御的关键酶。据认为在诸如急性炎性组织损伤和慢性炎性状况的情况下起致病作用。然而，缺乏对炎症部位iNOS和MPO之间相互关系的详细了解。我们使用直接光谱，HPLC和选择性NO电极测量来确定iNOS和MPO之间存在相互依存的关系，以及MPO / H_2O_2系统在上调发炎部位发生的iNOS催化活性中的作用。 MPO / H_2O_2系统从iNOS环境中清除游离NO可以恢复iNOS将L-精氨酸转化为产物（NO）的全部能力，这可以通过瓜氨酸和亚硝酸盐/硝酸盐生产速率的增加来判断。对iNOS催化机制和功能的研究对于更根本地了解这些因素至关重要，这些因素决定着人类健康和疾病中依赖iNOS的过程。

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