Molecular network analysis in pleiotropic effects of statin: an experimental elucidation of the pharmacologic action from protein-protein interaction analysis
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- Shiota Masayuki
- Department of Pharmacology, Osaka City University Medical School, Japan
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- Kusakabe Hiromi
- Department of Pharmacology, Osaka City University Medical School, Japan
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- Hikita Yuko
- Department of Pharmacology, Osaka City University Medical School, Japan
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- Nakao Takafumi
- Department of Pharmacology, Osaka City University Medical School, Japan
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- Izumi Yasukatsu
- Department of Pharmacology, Osaka City University Medical School, Japan
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- Iwao Hiroshi
- Department of Pharmacology, Osaka City University Medical School, Japan
書誌事項
- タイトル別名
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- Pharmacogenomics of Cardiovascular Pharmacology: Molecular Network Analysis in Pleiotropic Effects of Statin - an Experimental Elucidation of the Pharmacologic Action From Protein-Protein Interaction Analysis
- Pharmacogenomics of Cardiovascular Pharmacology: Molecular Network Analysis in Pleiotropic Effects of Statin — an Experimental Elucidation of the Pharmacologic Action From Protein-Protein Interaction Analysis
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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.<br>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 107 (1), 15-19, 2008
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680154936448
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- NII論文ID
- 10024320291
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 9500640
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- 抄録ライセンスフラグ
- 使用不可