Differential expression of proteins in fetal brains of alcohol-treated prenatally C57BL/6 mice: a proteomic investigation.
Differential expression of proteins in fetal brains of alcohol-treated prenatally C57BL/6 mice: a proteomic investigation.
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DOI：
10.1002/elps.200900385
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发表时间：
2010-01
期刊：
影响因子：
2.9
通讯作者：
Mechref, Yehia
中科院分区：
文献类型：
--
作者：
Sari, Youssef;Zhang, Min;Mechref, Yehia
已知酒精会阻碍中枢神经系统的生长，并通过细胞凋亡诱导神经变性。我们以前已经表明，适度的产前酒精暴露会导致不同发育阶段的大脑缺陷。在这项研究中，我们进一步的蛋白质组结构的特点，乙醇致畸作用在早期胎脑发育过程中使用色谱结合串联质谱（LC-MS/MS）系统。妊娠C57 BL/6小鼠从胚胎第7天（E7）至E13暴露于25%乙醇衍生卡路里（ALC）或成对喂养（PF）流质饮食。在E13时，从每组5只母兽中采集胎仔脑。将单个脑匀浆，然后将提取的蛋白质用胰蛋白酶消化并通过LC-MS/MS进行分析。对从ALC和PF组的胎脑提取的蛋白质组进行无标记定量蛋白质组学分析。这些分析表明，产前酒精暴露诱导线粒体酶的表达显着下调（p < 0.001），包括ADP/ATP移位酶1，ATP合成酶亚基α和泛喹啉-细胞色素-c还原酶。此外，在细胞凋亡中起作用的线粒体载体同源物1在ALC组中显著下调（p < 0.001）。此外，在显著下调（p < 0.001）的胞质蛋白中有Bcl-2、14-3-3蛋白和钙调蛋白。观察到对胎儿脑发育至关重要的蛋白质的显著下调（p < 0.001），例如抑制素和神经元迁移蛋白doublecortin。这些发现提供了信息的可能机制的影响，产前酒精暴露在胚胎早期阶段。
Alcohol is known to impede the growth of the central nervous system and to induce neurodegeneration through cellular apoptosis. We have previously shown that moderate prenatal alcohol exposure results in brain defects at different stages of development. In this study, we further characterize the proteomic architecture underlying ethanol teratogenesis during early fetal brain development using chromatography in conjunction with a tandem mass spectrometry (LC-MS/MS) system. Pregnant C57BL/6 mice were exposed from embryonic day 7 (E7) to E13 with either a 25% ethanol derived calorie (ALC) or pair-fed (PF) liquid diets. At E13, fetal brains were collected from 5 dams for each group. Individual brains were homogenized and the extracted proteins were then tryptically digested and analyzed by LC-MS/MS. Label-free quantitative proteomic analyses were performed on proteomes extracted from fetal brains of both ALC and PF groups. These analyses demonstrated that prenatal alcohol exposure induced significant down-regulation (p < 0.001) of the expression of mitochondrial enzymes including ADP/ATP translocase 1, ATP synthase subunit α and ubiquinol-cytochrome-c reductases. In addition, mitochondrial carrier homolog 1, which plays a role in apoptosis, was significantly down-regulated (p < 0.001) in the ALC group. Moreover, among the cytosolic proteins that were significantly down-regulated (p < 0.001) are Bcl-2, 14-3-3 protein and calmodulin. Significant down-regulation (p < 0.001) of proteins that are critical for fetal brain development was observed such as prohibitin and neuronal migration protein doublecortin. These findings provide information about possible mechanisms underlying the effects of prenatal alcohol exposure during early embryonic stage.
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影响因子：
2.9
作者：
BARRON, S;GAGNON, WA;RILEY, EP
通讯作者：
RILEY, EP
影响因子：
2.3
作者：
BONTHIUS, DJ;GOODLETT, CR;WEST, JR
通讯作者：
WEST, JR
影响因子：
2.9
作者：
KORNGUTH, SE;RUTLEDGE, JJ;YOUNG, B
通讯作者：
YOUNG, B
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
DOI：
10.1111/j.1530-0277.2003.tb04402.x
发表时间：
2003-04-01
影响因子：
3.2
作者：
Heaton, MB;Moore, DB;Shaw, G
通讯作者：
Shaw, G