VPA-related axial skeletal defects and apoptosis: A proposed event cascade
VPA-related axial skeletal defects and apoptosis: A proposed event cascade
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DOI：
10.1016/j.reprotox.2009.10.004
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Menegola, Elena
中科院分区：
文献类型：
--
作者：
Di Renzo, Francesca;Broccia, Maria Luisa;Menegola, Elena
VPA轴向畸形与胚胎体节组蛋白乙酰化有关。在癌症中，组蛋白超乙酰化激活细胞凋亡。为了验证细胞凋亡是否涉及体节异常，评价VPA暴露的胚胎的DNA片段化和促凋亡蛋白（p53、乙酰化p53、半胱天冬酶3）和抗细胞凋亡蛋白（Sirt 1）的表达。处理后3、5、9或24 h收集胚胎，进行细胞凋亡或蛋白质分析，在体节水平观察到一系列事件，并提出与VPA诱导的轴向骨骼缺陷有关：p53增加（3 h），DNA断裂（9 h），异常（24 h）。TSA，作为替代HDAC抑制剂，诱导细胞凋亡和体节异常，加强了我们假设的HDAC抑制和轴向缺陷之间的联系。(C)2009 Elsevier Inc. All rights reserved.
VPA axial malformations are related to embryonic somitic histone hyperacetylation. In cancer, histone hyperacetylation activates apoptosis. To verify if apoptosis is involved in somitic abnormalities, VPA-exposed embryos were evaluated for DNA fragmentation and for pro- (p53, acetylated p53, caspase 3) and anti-apoptotic (Sirt 1) protein expression.Pregnant mice were i.p. dosed on day 8 with VPA 400 mg/kg or TSA (16 mg/kg). Embryos, collected 3, 5, 9 or 24 h after treatment, were examined and processed for apoptosis or protein analysis.An event cascade has been observed at the level of somites and proposed as related to VPA-induced axial skeletal defects: increased p53 (3 h), DNA fragmentation (9 h), abnormalities (24 h). TSA, used as alternative HDAC inhibitor, induced apoptosis and somitic abnormalities, strengthening our hypothesized link between HDAC inhibition and axial defects. (C) 2009 Elsevier Inc. All rights reserved.