首页> 外文期刊>Reproductive toxicology >Valproic acid-induced DNA damage increases embryonic p27(KIP1) and caspase-3 expression: a mechanism for valproic-acid induced neural tube defects.
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Valproic acid-induced DNA damage increases embryonic p27(KIP1) and caspase-3 expression: a mechanism for valproic-acid induced neural tube defects.

机译:丙戊酸引起的DNA损伤增加了胚胎p27(KIP1)和caspase-3的表达:丙戊酸引起的神经管缺陷的机制。

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摘要

Valproic acid is a commonly prescribed antiepileptic agent that causes birth defects including neural tube defects. The purpose of this study was to measure DNA damage and downstream changes in cell cycle inhibitors and apoptosis to further elucidate the molecular changes that occur following VPA exposure. Pregnant CD-1 mice were administered a teratogenic dose of VPA (400mg/kg) on gestational day 9 (plug=day 1) and embryos extracted 0.5, 1, 3, 6, and 24h after injection. Western blotting and immunohistochemistry were performed for gammaH2A.X, p21(WAF1/CIP1), p27(KIP1), and cleaved caspase-3. A rapid increase in gammaH2A.X expression was observed a half hour following VPA exposure, followed by a subsequent decrease. p27(KIP1)and cleaved caspase-3 expression was significantly increased 3 and 6h following VPA exposure. Immunohistochemistry revealed increased staining for gammaH2A.X, p27(KIP1), and cleaved caspase 3 in the head, confirming our hypothesis that DNA damage, cell cycle inhibition, and apoptosis are induced by VPA.
机译:丙戊酸是通常处方的抗癫痫药,会引起出生缺陷,包括神经管缺陷。这项研究的目的是测量DNA损伤以及细胞周期抑制剂和细胞凋亡的下游变化,以进一步阐明VPA暴露后发生的分子变化。妊娠CD-1小鼠在妊娠第9天(栓塞=第1天)接受了致畸剂量的VPA(400mg / kg),注射后0.5、1、3、6和24h提取了胚胎。对gammaH2A.X,p21(WAF1 / CIP1),p27(KIP1)和裂解的caspase-3进行蛋白质印迹和免疫组化分析。 VPA暴露半小时后,观察到gammaH2A.X表达迅速增加,随后下降。 VPA暴露3和6小时后,p27(KIP1)和裂解的caspase-3表达显着增加。免疫组织化学显示,头部的gammaH2A.X,p27(KIP1)和caspase 3裂解染色增加,这证实了我们的假设,即VPA诱导DNA损伤,细胞周期抑制和细胞凋亡。

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