Oxidative Stress and Apoptosis in Benzo[a]pyrene-Induced Neural Tube Defects.
Oxidative Stress and Apoptosis in Benzo[a]pyrene-Induced Neural Tube Defects.
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苯并[a]芘诱导的神经管缺陷中的氧化应激和细胞凋亡
DOI：
10.1016/j.freeradbiomed.2018.01.004
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发表时间：
2018-02-20
影响因子：
7.4
通讯作者：
Greene ND
中科院分区：
文献类型：
--
作者：
Lin S;Ren A;Wang L;Huang Y;Wang Y;Wang C;Greene ND
神经管缺陷（NTD）是最常见和最严重的先天性畸形之一，是由早期发育过程中神经管的不完全闭合引起的。母亲暴露于多环芳烃（PAH）已被认为是NTDs的危险因素，以往的研究表明，PAH暴露和NTDs之间的关联的机制可能涉及氧化应激和细胞凋亡。本研究旨在探讨母体苯并[α]芘（BaP）暴露对小鼠神经管闭合的直接影响，并结合动物实验和人体实验研究其机制。我们发现，从胚胎第7天开始，以250 mg kg-1的剂量腹腔注射BaP诱导ICR小鼠NTDs（13.3%的频率）。BaP暴露显着增加与氧化应激相关的基因Cyp 1a 1、Sod 1和Sod 2的表达，同时抑制Gpx 1。在处理的胚胎的神经上皮细胞中观察到细胞凋亡增加和切割的caspase-3蛋白表达增加。维生素E预处理，添加到食物中，显着防止BaP诱导的NTDs（1.4%的频率）（P < 0.05）。维生素E也部分正常化BaP处理的胚胎中的氧化应激相关基因表达和过度凋亡。对人类神经组织的检查显示，蛋白质羰基和细胞凋亡水平的增加与母体暴露于多环芳烃和NTDs的风险有关。总的来说，这些结果表明，苯并（a）芘暴露可诱导NTDs，这可能涉及增加氧化应激和细胞凋亡，而维生素E可能具有保护作用。腹腔注射苯并（a）芘可诱导胎鼠神经管畸形（NTDs）。母体苯并（a）芘暴露改变了氧化应激相关基因的表达并诱导了胎鼠细胞凋亡。维生素E挽救BaP诱导的胎鼠NTDs可能部分通过其抗氧化和抗凋亡特性实现。PAH浓度与人母体血清中的蛋白质羰基（PC）水平相关。人胎儿神经组织中PC和细胞凋亡的升高与NTD风险的增加相关。
Neural tube defects (NTDs) are among the most common and severe congenital malformations and result from incomplete closure of the neural tube during early development. Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to be a risk factor for NTDs and previous studies imply that the mechanism underlying the association between PAH exposure and NTDs may involve oxidative stress and apoptosis. The objectives of this study were to investigate whether there is a direct effect of maternal benzo[α] pyrene (BaP) exposure on the closure of the neural tube in mice, and to examine the underlying mechanisms by combining animal experiments and human subject studies. We found that intraperitoneal injection of BaP from embryonic day 7 at a dose of 250 mg kg-1 induced NTDs (13.3% frequency) in ICR mice. BaP exposure significantly increased expression of genes associated with oxidative stress, Cyp1a1, Sod1 and Sod2, while repressing Gpx1. Elevated apoptosis and higher protein expression of cleaved caspase-3 in the neuroepithelium of treated embryos were observed. Pre-treatment with vitamin E, added to food, significantly protected against BaP-induced NTDs (1.4% frequency) (P < 0.05). Vitamin E also partly normalized oxidative stress related gene expression and excess apoptosis in BaP-treated embryos. Examination of human neural tissues revealed that increased levels of protein carbonyl and apoptosis were related with maternal exposure to PAHs and the risk of NTDs. Collectively, these results suggest that BaP exposure could induce NTDs and that this may involve increased oxidative stress and apoptosis, while vitamin E may have a protective effect. Intraperitoneal BaP injection induced neural tube defects (NTDs) in foetal mice. Maternal BaP exposure altered oxidative stress related gene expression and induced apoptosis in foetal mice. Vitamin E rescued BaP-induced NTDs in foetal mice may partly realized via its antioxidative and anti-apoptotic properties. PAH concentrations were associated with protein carbonyl (PC) levels in human maternal serum. Elevated PC and apoptosis in human foetal neural tissues were associated with increased NTD risk.
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影响因子：
4.5
作者：
Ben Slima A;Ali MB;Barkallah M;Traore AI;Boudawara T;Allouche N;Gdoura R
通讯作者：
Gdoura R
影响因子：
158.5
作者：
CZEIZEL, AE;DUDAS, I
通讯作者：
DUDAS, I
影响因子：
3.3
作者：
Briedé, JJ;Godschalk, RWL;Kleinjans, JCS
通讯作者：
Kleinjans, JCS
影响因子：
9.8
作者：
Betteridge, DJ
通讯作者：
Betteridge, DJ
DOI：
10.1073/pnas.83.5.1490
发表时间：
1986-03-01
影响因子：
11.1
作者：
BOREK, C;ONG, A;BIAGLOW, JE
通讯作者：
BIAGLOW, JE