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

Journal of Pharmacological Sciences

Hiroshi Iwao¹  Yuko Hikita¹  Hiromi Kusakabe¹  Yasukatsu Izumi¹  Masayuki Shiota¹  Takafumi Nakao¹ 

[1] Department of Pharmacology, Osaka City University Medical School, Japan

关键词: network analysis;    interaction;    statin;    pleiotropic effect;    Akt;    pharmacogenomics;   

DOI  :  10.1254/jphs.08R01FM

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 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.

【 授权许可】

Unknown