Ethanol influences on Bax translocation, mitochondrial membrane potential, and reactive oxygen species generation are modulated by vitamin E and brain-derived neurotrophic factor.
Ethanol influences on Bax translocation, mitochondrial membrane potential, and reactive oxygen species generation are modulated by vitamin E and brain-derived neurotrophic factor.
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DOI：
10.1111/j.1530-0277.2011.01445.x
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Siler-Marsiglio K
中科院分区：
文献类型：
--
作者：
Heaton MB;Paiva M;Siler-Marsiglio K
本研究探讨了乙醇对细胞内事件的影响，这些事件使发育中的神经元易于凋亡，以及抗氧化剂α-生育酚（维生素E）和神经营养素脑源性神经营养因子（BDNF）调节这些效应的能力。（1）乙醇诱导的促凋亡Bax蛋白向线粒体膜的移位，这是启动凋亡性细胞死亡的关键上游事件;（2）乙醇暴露导致的线粒体膜电位（MMP）的破坏，这是触发凋亡级联的重要过程;以及（3）作为乙醇暴露的函数的破坏性活性氧物质（ROS）的产生。这些相互作用进行了研究，在培养的出生后第8天的新生大鼠小脑颗粒细胞，一个人口易受发育乙醇暴露在体内和体外。Bax的线粒体易位进行了分析，通过亚细胞分级，然后通过蛋白质印迹，和线粒体膜的完整性进行了测定，使用亲脂性染料，JC-1，其表现出潜在的依赖性积累在线粒体膜的功能的MMP。短暂的乙醇暴露在这些制剂中沉淀Bax易位，但维生素E和BDNF都将这种作用降低到对照水平。乙醇处理也导致了MMP的紊乱，并且这种作用被抗氧化剂和神经营养因子减弱。在这些细胞中，短暂的乙醇暴露增强了ROS的产生，但通过与维生素E或BDNF共同治疗，这些有害自由基的产生减少到对照水平。这些结果表明，抗氧化剂和神经营养因子都有可能改善乙醇神经毒性，并建议可能的干预措施，可以实施预防或减轻严重程度的损害性影响的乙醇在发展中的中枢神经系统中看到的胎儿酒精综合征（FAS）。
This study investigated ethanol influences on intracellular events which predispose developing neurons toward apoptosis, and the capacity of the antioxidant α-tocopherol (vitamin E) and the neurotrophin brain-derived neurotrophic factor (BDNF) to modulate these effects. Assessments were made of the following: (1) ethanol-induced translocation of the pro-apoptotic Bax protein to the mitochondrial membrane, a key upstream event in the initiation of apoptotic cell death; (2) disruption of the mitochondrial membrane potential (MMP) as a result of ethanol exposure, an important process in triggering the apoptotic cascade; and (3) generation of damaging reactive oxygen species (ROS) as a function of ethanol exposure. These interactions were investigated in cultured postnatal day 8 neonatal rat cerebellar granule cells, a population vulnerable to developmental ethanol exposure in vivo and in vitro. Bax mitochondrial translocation was analyzed via subcellular fractionation followed by Western blot, and mitochondrial membrane integrity was determined using the lipophilic dye, JC-1, which exhibits potential-dependent accumulation in the mitochondrial membrane as a function of the MMP. Brief ethanol exposure in these preparations precipitated Bax translocation, but both vitamin E and BDNF reduced this effect to control levels. Ethanol treatment also resulted in a disturbance of the MMP, and this effect was blunted by the antioxidant and the neurotrophin. ROS generation was enhanced by a short ethanol exposure in these cells, but the production of these harmful free radicals was diminished to control levels by co-treatment with either vitamin E or BDNF. These results indicate that both antioxidants and neurotrophic factors have the potential to ameliorate ethanol neurotoxicity, and suggest possible interventions which could be implemented in preventing or lessening the severity of the damaging effects of ethanol in the developing central nervous system seen in the fetal alcohol syndrome (FAS).
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影响因子：
8
作者：
de la Monte, SM;Wands, JR
通讯作者：
Wands, JR
DOI：
10.1016/0736-5748(91)90041-j
发表时间：
1991-01-01
影响因子：
1.8
作者：
BRODIE, C;KENTROTI, S;VERNADAKIS, A
通讯作者：
VERNADAKIS, A
DOI：
10.1016/j.molbrainres.2004.06.034
发表时间：
2004-10-22
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ge, Y;Belcher, SA;Light, KE
通讯作者：
Light, KE
p53对于受TRKA和p75神经营养蛋白受体调节的发育神经元死亡至关重要。
影响因子：
7.8
作者：
Aloyz, R S;Bamji, S X;Pozniak, C D;Toma, J G;Atwal, J;Kaplan, D R;Miller, F D
通讯作者：
Miller, F D
DOI：
10.1016/s0169-328x(97)00173-3
发表时间：
1997-10-15
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Gabaizadeh, R;Staecker, H;VandeWater, TR
通讯作者：
VandeWater, TR