• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Hypochlorite-oxidized low density lipoproteins reduce production and bioavailability of nitric oxide in RAW 264.7 macrophages by distinct mechanisms.
【24h】

Hypochlorite-oxidized low density lipoproteins reduce production and bioavailability of nitric oxide in RAW 264.7 macrophages by distinct mechanisms.

机译：次氯酸盐氧化的低密度脂蛋白通过不同的机制降低了RAW 264.7巨噬细胞中一氧化氮的产生和生物利用度。

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

Oxidative modification of low density lipoproteins is thought to play a pivotal role in the development and exacerbation of atherosclerosis and atherogenesis, and is believed to be closely associated with alterations in the vascular production of nitric oxide (NO). Previous work has shown that several products emerging from lipid peroxidation (e.g. lipid hydroperoxides, lysophospholipids, oxidized cholesterol) are able to reduce NO production in macrophages. The naturally occurring oxidant hypochlorite has been shown to be responsible for the in vivo formation of hypochlorite-oxidized LDL and such OxLDL are known to lack lipid peroxidation products. In this work we demonstrate that hypochlorite-oxidized LDL mediate profound effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. By means of the membrane-permeable NO indicator 4,5-diaminofluorescein diacetate, we are able to show decreased levels of intracellular authentic nitric oxide following incubation with hypochlorite-oxidized LDL. The observed effects are dose-dependent and comparable to results obtained in the presence of the NOS inhibitor NG-monomethyl-L-arginine. This marked reduction of intracellular NO is accompanied by a dose-dependent inhibition of inducible nitric oxide synthase (iNOS) protein and mRNA expression. Furthermore, hyp-OxLDL lead to the generation of peroxynitrite, thereby also reducing bioavailability of NO. By mediating these effects on production and bioavailability of NO, hyp-OxLDL might also contribute to atherogenesis by reducing the antiatherogenic effects of nitric oxide.
机译：低密度脂蛋白的氧化修饰被认为在动脉粥样硬化和动脉粥样硬化的发展和恶化中起关键作用，并且被认为与一氧化氮（NO）血管生成的改变密切相关。先前的工作表明，脂质过氧化作用产生的几种产物（例如脂质氢过氧化物，溶血磷脂，氧化胆固醇）能够减少巨噬细胞中NO的产生。已经证明天然存在的氧化剂次氯酸盐负责体内次氯酸盐氧化的LDL的形成，并且已知这种OxLDL缺乏脂质过氧化产物。在这项工作中，我们证明了次氯酸盐氧化的LDL对RAW 264.7巨噬细胞中脂多糖诱导的一氧化氮产生介导了深远的影响。借助可透过膜的NO指示剂4,5-二氨基荧光素二乙酸酯，在与次氯酸盐氧化的LDL孵育后，我们能够显示出降低的细胞内真实一氧化氮水平。观察到的效果是剂量依赖性的，并且与在NOS抑制剂NG-单甲基-L-精氨酸存在下获得的结果相当。细胞内NO的显着减少伴随着剂量依赖性抑制可诱导型一氧化氮合酶（iNOS）蛋白和mRNA表达。此外，hyp-OxLDL导致过亚硝酸盐的生成，从而也降低了NO的生物利用度。通过介导这些对NO产生和生物利用度的影响，hyp-OxLDL也可能通过降低一氧化氮的抗动脉粥样硬化作用而促进动脉粥样硬化的形成。

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