...
首页> 外文期刊>Journal of pharmacological sciences. >Pharmacogenomics of Cardiovascular Pharmacology: Molecular Network Analysis in Pleiotropic Effects of Statin — an Experimental Elucidation of the Pharmacologic Action From Protein-Protein Interaction Analysis
【24h】

Pharmacogenomics of Cardiovascular Pharmacology: Molecular Network Analysis in Pleiotropic Effects of Statin — an Experimental Elucidation of the Pharmacologic Action From Protein-Protein Interaction Analysis

机译:心血管药理学的药理基因组学:他汀多效性的分子网络分析-从蛋白质-蛋白质相互作用分析中阐明药理作用的实验性解释

获取原文
           

摘要

References(37) Cited-By(9) The ebb and flow of cellular life depends largely on signaling pathways and networks, which are regulated by specific protein-protein interactions. These interactions often involve assembly of large signaling complexes containing many different protein kinases, protein phosphatases, their substrates, and scaffold proteins. Identification of protein complexes is the key to understanding cellular functions. One of the techniques used for the isolation of protein complexes is the affinity purification system. Inhibitors of 3-hydroxyl-3-methyglutaryl coenzyme A (HMG-CoA) reductase (i.e., statins) exert cholesterol-independent vasoprotective effects that are mediated, in part, through the activation of Akt. However, the molecular mechanism remains unknown. To elucidate the molecular mechanisms of the pleioptropic effects of statins, we searched for the binding molecule of Akt1 by using a combined mass spectrometry and affinity purification strategy. By this technique, we identified the protein-protein interactions of 23 proteins from statin-treated rat aortic endothelial cells (rAECs). Our results suggest that this approach is very effective and statin activates many Akt down-stream targets, not only endothelial nitric oxide synthase (eNOS). The methodology presented here would provide a new tool for chemical proteomics in medicinal science.
机译:参考文献(37)被引用的文献(9)细胞生命的起伏在很大程度上取决于信号传导途径和网络,这些信号传导途径和网络受到特定蛋白质-蛋白质相互作用的调节。这些相互作用通常涉及包含许多不同蛋白激酶,蛋白磷酸酶,其底物和支架蛋白的大型信号复合物的组装。蛋白质复合物的鉴定是了解细胞功能的关键。用于分离蛋白质复合物的技术之一是亲和纯化系统。 3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶(即他汀类)的抑制剂发挥非胆固醇依赖性的血管保护作用,这种作用部分是通过激活Akt介导的。但是,分子机制仍然未知。为了阐明他汀类药物的多效作用的分子机制,我们通过结合使用质谱和亲和纯化策略来搜索Akt1的结合分子。通过这种技术,我们从他汀类药物治疗的大鼠主动脉内皮细胞(rAEC)中鉴定了23种蛋白质的蛋白质-蛋白质相互作用。我们的结果表明,这种方法非常有效,他汀类药物不仅激活内皮型一氧化氮合酶(eNOS),还激活了许多Akt下游靶标。本文介绍的方法学将为药物科学中的蛋白质组学提供新的工具。

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