Activity-dependent neurotrophic factor-derived peptide prevents alcohol-induced apoptosis, in part, through Bcl2 and c-Jun N-terminal kinase signaling pathways in fetal brain of C57BL/6 mouse.
Activity-dependent neurotrophic factor-derived peptide prevents alcohol-induced apoptosis, in part, through Bcl2 and c-Jun N-terminal kinase signaling pathways in fetal brain of C57BL/6 mouse.
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DOI：
10.1016/j.neuroscience.2011.11.061
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发表时间：
2012-01-27
期刊：
影响因子：
3.3
通讯作者：
Ge, S.
中科院分区：
文献类型：
--
作者：
Sari, Y.;Weedman, J. M.;Ge, S.
已知胎儿酒精暴露会引起胎儿大脑发育的改变。在这项研究中，我们专注于使用ADNF-9（一种来自活动依赖性神经营养因子的肽）对酒精暴露的神经保护作用。我们使用了胎儿酒精暴露的小鼠模型，以确定细胞内机制的神经保护作用的ADNF-9。在胚胎第7天（E7），将体重匹配的妊娠雌性动物分配到以下组：（1）25%（4.49%，v/v）乙醇衍生卡路里的乙醇液体饮食（ALC）;（2）成对喂养对照（PF）;（3）ALC与施用（i. p.）的ADNF-9（ALC/ADNF-9）;和（4）配对喂养联合施用（i. p.）的ADNF-9（PF/ADNF-9）。在E13，收集胎脑，称重，并使用TUNEL测定法测定细胞凋亡。Bcl 2蛋白和磷酸-c-Jun N-末端激酶（JNK）水平分别用Western blot和酶免疫测定法测定。ADNF-9给药显著防止了酒精诱导的胎脑重量减少。此外，ADNF-9阻止了酒精诱导的大脑皮层原基和神经节隆起细胞死亡的增加。线粒体蛋白质组分的Western印迹分析显示，ADNF-9管理防止酒精诱导的Bcl 2水平的降低。此外，对上游信号通路中的蛋白质的分析显示，ADNF-9下调JNK的磷酸化。这些数据表明线粒体Bcl 2通路和JNK上游信号通路是ADNF-9的细胞内靶点。ADNF-9的神经保护作用机制为针对涉及线粒体功能障碍的酒精诱导的神经损伤的潜在治疗提供了方向。
Fetal alcohol exposure is known to induce alteration in fetal brain development. In this study, we focused on neuroprotection against the effects of alcohol exposure using ADNF-9, a peptide derived from activity-dependent neurotrophic factor. We used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying the neuroprotective effects of ADNF-9. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) of 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control (PF); (3) ALC combined with administration (i.p.) of ADNF-9 (ALC/ADNF-9); and (4) pair-fed combined with administration (i.p.) of ADNF-9 (PF/ADNF-9). On E13, fetal brains were collected, weighed, and apoptosis was determined using TUNEL assay. Bcl2 protein and phospho-c-Jun N-terminal kinase (JNK) levels were determined using Western blot and enzyme immunometric assay, respectively. ADNF-9 administration significantly prevented alcohol-induced reductions in fetal brain weight. In addition, ADNF-9 prevented an alcohol-induced increase in cell death in the primordium of the cerebral cortex and ganglionic eminence. Western blot analysis of the mitochondrial protein fractions revealed that ADNF-9 administration prevented an alcohol-induced reduction in the Bcl2 level. Moreover, an analysis of the proteins in the upstream signaling pathway revealed that ADNF-9 down-regulated the phosphorylation of JNK. These data indicate that the mitochondrial Bcl2 pathway and JNK upstream signaling pathway are the intracellular targets of ADNF-9. The neuroprotective mechanism of action of ADNF-9 provides a direction for potential therapeutics against alcohol-induced neural damage involving mitochondrial dysfunction.
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影响因子：
3.3
作者：
Sari, Y.;Chiba, T.;Yamada, M.;Rebeca, G. V.;Aiso, S.
通讯作者：
Aiso, S.
影响因子：
4.7
作者：
Bassan, M;Zamostiano, R;Gozes, I
通讯作者：
Gozes, I
DOI：
10.1111/j.1530-0277.1998.tb03658.x
发表时间：
1998-04-01
影响因子：
3.2
作者：
Roebuck, TM;Mattson, SN;Riley, EP
通讯作者：
Riley, EP
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