Antioxidant and neuroprotective properties of N-arachidonoyldopamine
Antioxidant and neuroprotective properties of N-arachidonoyldopamine
复制标题
DOI：
10.1016/j.neulet.2007.11.010
复制
发表时间：
2008-01-24
影响因子：
2.5
通讯作者：
Bezuglov, Vladimir V.
中科院分区：
文献类型：
--
作者：
Bobrov, Mikhail Yu.;Lizhin, Anatoly A.;Bezuglov, Vladimir V.
N-酰基多巴胺被认为是大鼠脑内的内源性物质。其中，N-花生四烯酸多巴胺（AADA）被鉴定为大麻素CBI和香草素TRPV 1受体配体。这类化合物的生理意义还知之甚少。在这项研究中，我们描述了AADA作为抗氧化剂和神经保护剂的新特性。首先在galvinoxyl测定中测试AADA及其类似物的抗氧化潜力。结果发现，N-酰基多巴胺是有效的抗氧化剂和多巴胺的酚部分中的游离羟基的数量是必不可少的活性。AADA剂量依赖性（0.1-10 μ M）保护培养的小脑颗粒神经元（CGN）在过氧化氢诱导的氧化应激模型。另一种内源性物质N-油酰多巴胺在这些条件下的效力要低得多，而天然抗氧化剂α-生育酚则无活性。在该试验中，AADA降低了CGN制剂中的过氧化物水平，其神经保护作用不依赖于大麻素/香草素受体阻断。AADA（10 μ M）也保护CGN免于K+/血清剥夺和谷氨酸兴奋毒性诱导的死亡。这些数据表明，AADA可能作为内源性抗氧化剂在不同的病理条件。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
N-Acyldopamines were recently described as putative endogenous substances in the rat brain. Among them, N-arachidonoyldopamine (AADA) was characterized as cannabinoid CBI and vanilloid TRPV1 receptor ligand. The physiological significance of such compounds is yet poorly understood. In this study, we describe the novel properties of AADA as antioxidant and neuroprotectant. Antioxidant potential of AADA and its analogs were first tested in the galvinoxyl assay. It was found that N-acyldopamines are potent antioxidants and that the number of free hydroxyl groups in the phenolic moiety of dopamine is essential for the activity. AADA dose dependently (0.1-10 mu M) protected cultured cerebellar granule neurons (CGN) in the model of oxidative stress induced by hydrogen peroxide. N-Oleoyldopamine, another endogenous substance, was much less potent in these conditions while the natural antioxidant a-tocopherol was inactive. In this test, AADA decreased the peroxide level in CGN preparations and its neuroprotection was independent of cannabinoid/vanilloid receptors blockade. AADA (10 mu M) also protected CGN from death induced by K+/serum deprivation and glutamate exitotoxicity. These data indicate that AADA may act as endogenous antioxidant in different pathological conditions. (C) 2007 Elsevier Ireland Ltd. All rights reserved.