...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Regulation of nitric oxide-responsive recombinant soluble guanylyl cyclase by calcium.
【24h】

Regulation of nitric oxide-responsive recombinant soluble guanylyl cyclase by calcium.

机译：钙对一氧化氮反应性重组可溶性鸟苷酸环化酶的调节。

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

Calcium (Ca2+) and cyclic GMP (cGMP) subserve antagonistic functions that are reflected in their coordinated reciprocal regulation in physiological systems. However, molecular mechanisms by which Ca2+ regulates cGMP-dependent signaling remain incompletely defined. In this study, the inhibition of recombinant nitric oxide (NO)-stimulated soluble guanylyl cyclase (SGC) by Ca2+ was demonstrated. The alpha- and beta-subunits of recombinant rat SGC were heterologously coexpressed in HEK 293 cells which do not express NO synthase, whose Ca2+-stimulated activity can confound the effects of that cation on SGC. Ca2+ inhibited basal and NO-stimulated SGC in a concentration- and guanine nucleotide-dependent fashion. This cation inhibited SGC in crude cell extracts and immunopurified preparations. Ca2+ lowered both the Vmax and Km of SGC via an uncompetitive mechanism through direct interaction with the enzyme. In intact HEK 293 cells, increases in the intracellular Ca2+ concentration induced by ionomycin, a Ca2+ ionophore, and thapsigargin, which releases intracellular stores of that cation, inhibited NO-stimulated intracellular cGMP accumulation. Similarly, carbachol-induced elevation of the intracellular Ca2+ concentration inhibited NO-stimulated intracellular cGMP accumulation in HEK 293 cells. These data demonstrate that SGC behaves as a sensitive Ca2+ detector that may play a central role in coordinating the reciprocal regulation of Ca2+- and cGMP-dependent signaling mechanisms.
机译：钙（Ca2 +）和环状GMP（cGMP）具有拮抗作用，在生理系统中它们的相互调节相互协调。然而，Ca 2+调节依赖cGMP的信号传导的分子机制仍未完全确定。在这项研究中，证明了Ca2 +对重组一氧化氮（NO）刺激的可溶性鸟苷环化酶（SGC）的抑制作用。重组大鼠SGC的α和β亚基在不表达NO合酶的HEK 293细胞中异源共表达，其Ca2 +刺激的活性可以混淆该阳离子对SGC的作用。 Ca2 +以浓度和鸟嘌呤核苷酸依赖性方式抑制基础和NO刺激的SGC。该阳离子抑制粗细胞提取物和免疫纯化制剂中的SGC。 Ca2 +通过与酶直接相互作用的非竞争性机制降低了SGC的Vmax和Km。在完整的HEK 293细胞中，由离子霉素，Ca2 +离子载体和毒胡萝卜素诱导的细胞内Ca2 +浓度增加，释放了该阳离子的细胞内存储，抑制了NO刺激的细胞内cGMP积累。同样，卡巴胆碱诱导的细胞内Ca2 +浓度升高抑制了HEK 293细胞中NO刺激的细胞内cGMP积累。这些数据表明，SGC充当敏感的Ca2 +检测器，在协调Ca2 +和cGMP依赖性信号传导机制的相互调节中可能起着核心作用。

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