Cannabidiol-2',6'-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro.
Cannabidiol-2',6'-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro.
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DOI：
10.1248/bpb.34.1252
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发表时间：
2011
影响因子：
2
通讯作者：
Aramaki H
中科院分区：
文献类型：
--
作者：
Takeda S;Hirayama A;Urata S;Mano N;Fukagawa K;Imamura M;Irii A;Kitajima S;Masuyama T;Nomiyama M;Tatei S;Tomita S;Kudo T;Noguchi M;Yamaguchi Y;Okamoto Y;Amamoto T;Fukunishi Y;Watanabe K;Omiecinski CJ;Aramaki H
15-脂氧合酶（15-LOX）是负责氧化低密度脂蛋白（ox-LDL）形成的关键酶之一，ox-LDL是动脉粥样硬化的主要原因。酶（15-LOX）和非酶（Cu2+）两种机制都被提出用于ox-LDL的产生。我们最近报道了大麻二酚-2 ',6 ' -二甲醚（CBDD）是一种选择性和有效的15- lox催化亚油酸氧化抑制剂（Takeda等人，Drug Metab）。Dispos。农业学报，37,1733-1737(2009))。在低密度脂蛋白中，亚油酸以胆固醇亚油酸酯的形式存在，这是酯化成胆固醇的主要脂肪酸，容易被15-LOX或Cu2+氧化修饰。在这项研究中，我们研究了CBDD对1)15-LOX催化的胆固醇亚油酸的氧化作用，以及2)15-LOX催化的ox-LDL形成与Cu2+介导的非酶促生成这一重要介质的效果。结果表明，CBDD是一种有效的选择性抑制剂，可抑制15-LOX途径产生的ox-LDL形成。这些研究表明，CBDD既是表征15- lox介导的ox-LDL形成的重要实验工具，也是治疗动脉粥样硬化的潜在有用的治疗剂。
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.
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影响因子：
2.7
作者：
Tanaka, K;Iguchi, H;Kojo, S
通讯作者：
Kojo, S
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CATHCART, MK
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作者：
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