Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults
Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults
复制标题
DOI：
10.1016/j.bcp.2006.11.003
复制
发表时间：
2007-02-15
影响因子：
5.8
通讯作者：
Akaike, Akinori
中科院分区：
文献类型：
--
作者：
Okawara, Mitsugi;Katsuki, Hiroshi;Akaike, Akinori
越来越多的证据表明，白藜芦醇（一种存在于多种膳食产品中的多酚化合物）具有细胞保护作用。值得注意的是，白藜芦醇。激活 NAD 依赖性组蛋白脱乙酰酶的 Sirtuin 家族，参与调节各种细胞过程，包括基因转录、DNA 修复和细胞凋亡。在这里，我们检查了白藜芦醇对器官型中脑切片培养中的多巴胺能神经元的神经保护作用。白藜芦醇和槲皮素（另一种激活去乙酰化酶的多酚）可防止多巴胺能神经元的减少以及由多巴胺能神经毒素 1-甲基-4-苯基吡啶 (MPP+) 诱导的切片中碘化丙啶摄取的增加。白藜芦醇还针对叠氮化钠（一种线粒体复合物 IV 抑制剂）和凝血酶（EC 号 3.4.21.5）（一种小胶质细胞激活剂）提供浓度依赖性神经保护作用。 Sirtuin 抑制剂如烟酰胺和 Sirtinol 不会减弱白藜芦醇对 MPP+ 细胞毒性的保护作用。相反，我们发现白藜芦醇可以防止活性氧的积累、细胞谷胱甘肽的消耗以及 MPP+ 诱导的细胞氧化损伤，表明抗氧化特性参与白藜芦醇的神经保护作用。另一方面，白藜芦醇以及沉默调节蛋白激活剂 NAD 抑制 DNA 烷化剂 N 甲基-N'-硝基-N-亚硝基胍 (MNNG) 的多巴胺能神经毒性。此外，MNNG 诱导的 p53 乙酰化增加（sirtuin 脱乙酰酶活性的代表性靶标）被白藜芦醇抑制。这些结果表明白藜芦醇可以对多巴胺能神经元发挥神经保护作用。抗氧化活性或沉默调节蛋白激活潜力可能在白藜芦醇针对不同类型损伤的神经保护作用中发挥重要作用。 (c) 2006 Elsevier Inc. 保留所有权利。
increasing lines of evidence show that resveratrol, a polyphenol compound contained in several dietary products, exhibits cytoprotective actions. Notably, resveratrol. activates sirtuin family of NAD-dependent histone deacetylases implicated in regulation of various cellular processes including gene transcription, DNA repair and apoptosis. Here we examined neuroprotective effect of resveratrol on dopaminergic neurons in organotypic midbrain slice culture. Resveratrol and quercetin, another sirtuin-activating polyphenol, prevented the decrease of dopaminergic neurons and the increase of propidium iodide uptake into slices induced by a dopaminergic neurotoxin 1-methyl-4-phenyl pyridinium (MPP+). Resveratrol also provided concentration-dependent neuroprotective effects against sodium azide, a mitochondrial complex IV inhibitor, and thrombin (EC number 3.4.21.5), a microglia-activating agent. Sirtuin inhibitors such as nicotinamide and sirtinol did not attenuate the protective effect of resveratrol against MPP+ cytotoxicity. Instead, we found that resveratrol prevented accumulation of reactive oxygen species, depletion of cellular glutathione, and cellular oxidative damage induced by MPP+, suggesting involvement of antioxidative properties in the neuroprotective action of resveratrol. on the other hand, resveratrol as well as a sirtuin activator NAD inhibited dopaminergic neurotoxicity of a DNA alkylating agent, Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). Moreover, MNNG-induced increase in acetylation of p53, a representative target of sirtuin deacetylase activity, was suppressed by resveratrol. These results indicate that resveratrol can exert neuroprotective actions in dopaminergic neurons. Either antioxidative activity or sirtuin-activating potential may play an important role in the neuroprotectice actions of resveratrol against different kinds of insults. (c) 2006 Elsevier Inc. All rights reserved.