Peptide-mediated protection from ethanol-induced neural tube defects
Peptide-mediated protection from ethanol-induced neural tube defects
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DOI：
10.1159/000084528
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Sulik, KK
中科院分区：
文献类型：
--
作者：
Chen, SY;Charness, ME;Sulik, KK
乙醇抑制L1介导的细胞粘附可能有助于与产前乙醇暴露相关的神经，行为和形态异常的频谱。我们先前表明，神经保护肽NAPVSIPQ（NAP）和SALLRSIPA（SAL）拮抗乙醇抑制L1粘附，并防止乙醇诱导的生长迟缓，在小鼠全胚胎培养。在这里，我们问NAP和SAL是否也防止乙醇引起的神经系统的主要畸形。将妊娠第8.0天（3-5体节）的C57 BL/6 J小鼠胚胎在对照培养基、100 mM乙醇和10（-10）M肽中生长6小时，然后在对照培养基中再维持20小时。在培养期结束时，仅检查具有18-19体节对的胚胎，并比较神经管闭合的程度。乙醇暴露导致神经管缺陷（NTDs）与总的书写困难和无脑畸形一致。与乙醇和L-NAP（所有L-氨基酸），D-NAP（所有D-氨基酸）或SAL的共孵育显着增加的百分比，胚胎已经开始关闭其神经褶皱在前脑/中脑交界处的水平或已经超过这个阶段的关闭。P7 A-NAP（NAPVSIAQ），缺乏神经保护活性，但保留了作为乙醇抑制L1粘附的拮抗剂的活性，可有效预防乙醇诱导的NTDs。相比之下，16 A-NAP（NAPVSAPQ），这表明降低的疗效作为乙醇拮抗剂，但保留其神经保护功效，并没有显着减少诱导NTD乙醇。这些研究结果表明，NAP和SAL的能力，以防止乙醇诱导的NTDs和支持的假设，即乙醇致畸是由乙醇抑制L1介导的细胞粘附的一部分。版权所有（c）2005 S. Karger AG，巴塞尔。
Ethanol inhibition of L1-mediated cell adhesion may contribute to the spectrum of neurological, behavioral and morphological abnormalities associated with prenatal ethanol exposure. We showed previously that the neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) antagonize ethanol inhibition of L1 adhesion and prevent ethanol-induced growth retardation in mouse whole embryo culture. Here we ask whether NAP and SAL also prevent ethanol-induced major malformations of the nervous system. Gestational day 8.0 (3-5 somites) C57BL/6J mouse embryos were grown for 6 h in control medium, 100 m M ethanol and 10(-10) M peptides and then maintained for an additional 20 h in control medium. At the end of the culture period, only embryos having 18-19 somite pairs were examined and compared for the degree of neural tube closure. Ethanol exposure resulted in neural tube defects (NTDs) consistent with total dysraphia and anencephaly. Co-incubation with ethanol and L-NAP (all L-amino acids), D-NAP (all D-amino acids) or SAL significantly increased the percentage of embryos that had begun to close their neural folds at the level of the forebrain/midbrain junction or that had progressed beyond this stage of closure. P7A-NAP (NAPVSIAQ), which lacks neuroprotective activity, but retains activity as an antagonist of ethanol inhibition of L1 adhesion, was effective in preventing ethanol-induced NTDs. In contrast, 16A-NAP (NAPVSAPQ), which shows reduced efficacy as an ethanol antagonist but retains its neuroprotective efficacy, did not significantly diminish the induction of NTDs by ethanol. These findings demonstrate the ability of NAP and SAL to prevent ethanol-induced NTDs and support the hypothesis that ethanol teratogenesis is caused in part by ethanol inhibition of L1-mediated cell adhesion. Copyright (c) 2005 S. Karger AG, Basel.