Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons
Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons
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DOI：
10.1016/j.brainres.2008.02.018
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发表时间：
2008-04-14
期刊：
影响因子：
2.9
通讯作者：
Druse, Mary J.
中科院分区：
文献类型：
--
作者：
Antonio, Angeline M.;Druse, Mary J.
众所周知，乙醇通过增加细胞凋亡损害发育中的神经系统。以前，本实验室报道，乙醇增强胎儿菱脑神经元的凋亡，并且凋亡增加与磷脂酰肌醇3-激酶途径的活性降低和促生存基因的下游表达相关。其他实验室已经表明，乙醇诱导发育中神经元凋亡的另一种机制是通过产生活性氧（ROS）和相关的氧化应激。本研究采用体外模型，探讨了几种抗氧化剂对乙醇相关凋亡的胎儿菱脑神经元的潜在神经保护作用。研究的抗氧化剂包括三种酚类物质：（-）-表没食子儿茶素-3-没食子酸酯（EGCG），一种在绿色茶中发现的类黄酮多酚;姜黄素，在姜黄中发现;白藜芦醇（3，5，4 '-三羟基芪），红葡萄酒的一种成分。另外的抗氧化剂，包括褪黑激素，天然存在的吲哚，和α-硫辛酸，天然存在的二硫醇，也进行了研究。这些研究表明，用75 mM乙醇处理胎儿菱形脑神经元24小时，导致凋亡神经元的百分比增加3倍。然而，与五种不同抗氧化剂中的任何一种共同处理这些培养物可以防止乙醇相关的细胞凋亡。抗氧化剂处理没有改变对照神经元中的凋亡程度，即，那些在没有乙醇的情况下培养的。这些研究表明，几类抗氧化剂可以对胎儿菱脑神经元乙醇相关的凋亡发挥神经保护作用。(C)2008 Elsevier B. V.保留所有权利。
It is well known that ethanol damages the developing nervous system by augmenting apoptosis. Previously, this laboratory reported that ethanol augments apoptosis in fetal rhombencephalic neurons, and that the increased apoptosis is associated with reduced activity of the phosphatidylinositol 3-kinase pathway and downstream expression of pro-survival genes. Other laboratories have shown that another mechanism by which ethanol induces apoptosis in developing neurons is through the generation of reactive oxygen species (ROS) and the associated oxidative stress. The present study used an in vitro model to investigate the potential neuroprotective effects of several antioxidants against ethanol-associated apoptosis in fetal rhombencephalic neurons. The investigated antioxidants included three phenolics: (-)-epigallocatechin-3-gallate (EGCG), a flavanoid polyphenol found in green tea; curcumin, found in tumeric; and resveratrol (3,5,4'-trihydroxystilbene), a component of red wine. Additional antioxidants, including melatonin, a naturally occurring indole, and a-lipoic acid, a naturally occurring dithiol, were also investigated. These studies demonstrated that a 24-hour treatment of fetal rhombencephalic neurons with 75 mM ethanol caused a 3-fold increase in the percentage of apoptotic neurons. However, co-treatment of these cultures with any of the five different antioxidants prevented ethanol-associated apoptosis. Antioxidant treatment did not alter the extent of apoptosis in control neurons, i.e., those cultured in the absence of ethanol. These studies showed that several classes of antioxidants can exert neuroprotection against ethanol-associated apoptosis in fetal rhombencephalic neurons. (C) 2008 Elsevier B.V. All rights reserved.