Activity-dependent neuroprotective protein-derived peptide, NAP, preventing alcohol-induced apoptosis in fetal brain of C57BL/6 mouse.
Activity-dependent neuroprotective protein-derived peptide, NAP, preventing alcohol-induced apoptosis in fetal brain of C57BL/6 mouse.
复制标题
DOI：
10.1016/j.neuroscience.2008.11.021
复制
发表时间：
2009-02-18
期刊：
影响因子：
3.3
通讯作者：
Sari, Y.
中科院分区：
文献类型：
--
作者：
Sari, Y.
已经使用先前被证明参与体外和体内神经保护作用的肽研究了可能预防产前酒精暴露影响的方法。我在这项研究中重点研究了其中一种肽的神经保护作用，以确定参与神经保护的下游信号通路。这种具有 NAPVSIPQ 序列的肽（称为 NAP）是活性依赖性神经保护蛋白的片段，对与酒精暴露相关的氧化应激具有有效的保护作用。在胚胎第 7 天 (E7)，体重匹配的 C57BL/6 怀孕雌性被分配到以下组：(1) 乙醇液体饮食组 (ALC) 25% (4.49%，v/v) 乙醇衍生热量，(2) 配对喂养 (PF) 对照组，(3) Chow 对照组，(4) 腹腔注射酒精的治疗组。注射d-NAP（ALC/d-NAP，20或30μg/20g体重），（5）PF/d-NAP对照组。 E13 时，收集胎儿大脑并进行 TdT 介导的 dUTP 缺口末端标记 (TUNEL) 染色、Caspase-3 比色测定和用于细胞色素 c 检测的 ELISA 测定。我的结果表明，NAP 显着阻止了酒精引起的胎儿大脑重量减轻。通过TUNEL染色测定细胞凋亡； NAP 给药显着阻止了酒精诱导的扣带皮层原基和基底神经节隆起中 TUNEL 阳性细胞的增加。对涉及 NAP 神经保护的下游信号通路的研究表明，该肽显着阻止酒精诱导的 E13 胎儿大脑中 caspase-3 浓度的增加。此外，细胞色素 c 的 ELISA 表明，NAP 显着阻止酒精诱导的胞质细胞色素 c 水平的增加和酒精诱导的线粒体细胞色素 c 水平的降低。这些数据提供了对 NAP 细胞内靶标及其下游作用机制的了解，这将为开发针对产前阶段酒精中毒的潜在疗法铺平道路。
Possible prevention of the effects of prenatal alcohol exposure has been investigated using peptides that were previously shown to be involved in neuroprotection both in vitro and in vivo. I focused in this study on investigating the neuro-protective effects of one of these peptides with regard to the determination of the downstream signaling pathways involved in neuroprotection. This peptide with the sequence NAPVSIPQ, known as NAP, a fragment of activity-dependent neuroprotective protein, demonstrated a potent protective effect against oxidative stress associated with alcohol exposure. On embryonic day 7 (E7), weight-matched C57BL/6 pregnant females were assigned the following groups: (1) Ethanol liquid diet group (ALC) 25% (4.49%, v/v) ethano-derived calories, (2) Pair-fed (PF) control group (3) Chow control group, (4) treatment groups with alcohol alongside i.p. injections of d-NAP (ALC/d-NAP, 20 or 30 μg/20 g body weight), (5) PF/d-NAP control group. On E13, fetal brains were collected and assayed for TdT-mediated dUTP nick end labeling (TUNEL) staining, caspase-3 colorimetric assay and ELISA for cytochrome c detection. My results show that NAP significantly prevented alcohol-induced weight reduction of the fetal brain. Apoptosis was determined by TUNEL staining; NAP administration significantly prevented alcohol-induced increases in TUNEL-positive cells in primordium cingulate cortex and basal ganglia eminence. The investigation of downstream signaling pathways involving NAP neuroprotection revealed that this peptide significantly prevented alcohol-induced increase in the concentrations of caspase-3 in E13 fetal brains. Moreover, ELISA for cytochrome c shows that NAP significantly prevented both alcohol-induced increases in the level of cytosolic cytochrome c and alcohol-induced decreases in the level of mitochondrial cytochrome c. These data provide an understanding of NAP intracellular target, and the downstream mechanisms of action that will pave a path toward potential therapeutics against alcohol intoxication during prenatal stages.
登录
查看更多内容
影响因子：
2.9
作者：
BARRON, S;GAGNON, WA;RILEY, EP
通讯作者：
RILEY, EP
DOI：
10.1111/j.1530-0277.1995.tb01624.x
发表时间：
1995-10-01
影响因子：
3.2
作者：
MIDDAUGH, LD;BOGGAN, WO
通讯作者：
BOGGAN, WO
影响因子：
4.7
作者：
Bassan, M;Zamostiano, R;Gozes, I
通讯作者：
Gozes, I
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