Cannabidiol-2',6'-dimethyl Ether as an Effective Protector of 15-Lipoxygenase-Mediated Low-Density Lipoprotein Oxidation in Vitro
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- Takeda Shuso
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Hirayama Akari
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Urata Shino
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Mano Nobutaka
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Fukagawa Keiko
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Imamura Midori
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Irii Ayumi
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Kitajima Satomi
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Masuyama Tomoko
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Nomiyama Mai
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Tatei Sachiko
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Tomita Saari
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Kudo Taichi
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Noguchi Momoko
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Yamaguchi Yasuhiro
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Okamoto Yoshiko
- Department of Molecular Biology, Daiichi University of Pharmacy
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- Amamoto Toshiaki
- NEUES Corporation
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- Fukunishi Yoshifumi
- Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST)
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- Watanabe Kazuhito
- Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
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- Omiecinski Curtis John
- Center for Molecular Toxicology and Carcinogenesis
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- Aramaki Hironori
- Department of Molecular Biology, Daiichi University of Pharmacy
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15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu2+) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2′,6′-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al., Drug Metab. Dispos., 37, 1733—1737 (2009)). In the LDL, linoleic acid is present as cholesteryl linoleate, the major fatty acid esterified to cholesterol, and is susceptible to oxidative modification by 15-LOX or Cu2+. In this investigation, we examined the efficacy of CBDD on i) 15-LOX-catalyzed oxygenation of cholesteryl linoleate, and ii) ox-LDL formation catalyzed by 15-LOX versus Cu2+-mediated non-enzymatic generation of this important mediator. The results obtained demonstrate that CBDD is a potent and selective inhibitor of ox-LDL formation generated by the 15-LOX pathway. These studies establish CBDD as both an important experimental tool for characterizing 15-LOX-mediated ox-LDL formation, and as a potentially useful therapeutic agent for treatment of atherosclerosis.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 34 (8), 1252-1256, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632733312
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- NII論文ID
- 130000936595
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 11174633
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- PubMed
- 21804214
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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
- Crossref
- PubMed
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