Nonylphenol induces the death of neural stem cells due to activation of the caspase cascade and regulation of the cell cycle
Nonylphenol induces the death of neural stem cells due to activation of the caspase cascade and regulation of the cell cycle
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DOI：
10.1046/j.1471-4159.2003.02270.x
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发表时间：
2004-03-01
影响因子：
4.7
通讯作者：
Kamisaki, Y
中科院分区：
文献类型：
--
作者：
Kudo, C;Wada, K;Kamisaki, Y
内分泌干扰物(EDs)是全世界非常关注的问题，因为它们对人类健康和野生动物都有不利影响。在本研究中，我们研究了内源性神经干细胞对小鼠神经干细胞增殖和存活的影响。与双酚A、邻苯二甲酸苄基正丁酯、邻苯二甲酸二丁酯和邻苯二甲酸二(2-乙基己基)酯不同，4-壬基苯酚作用24 h可抑制细胞生长，且呈浓度依赖性。此外，4-壬基酚作用于NSCs 12h后出现核固缩和DNA片段化(细胞凋亡所致的形态改变)，并在6h和9h后激活caspase-3。此外，4-壬基酚导致细胞在G(2)/M期界面聚集，下调细胞周期蛋白A和B1的蛋白水平，这两个蛋白是细胞周期从G(2)向M过渡的主要调控蛋白。综上所述，这些结果表明，与其他ED相比，4-壬基酚可能通过caspase级联反应和细胞周期停滞于G(2)/M期而表现出强大的细胞毒作用，并可能影响中枢神经系统的神经发生。
Endocrine disruptors (EDs) are a great concern throughout the world, because they have adverse effects on human health and wildlife. In the present study, we investigated the effects of EDs on the proliferation and survival of murine neural stem cells (NSCs). In contrast to bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester, the treatment of NSCs with 4-nonylphenol for 24 h inhibited cell growth in a concentration-dependent manner. In addition, treatment with 4-nonylphenol resulted in nuclear condensation and DNA fragmentation (morphological changes due to apoptosis) in NSCs after 12 h of exposure, and activated caspase-3 after 6 h and 9 h of exposure. Furthermore, an exposure to 4-nonylphenol led to the accumulation of cells at the G(2)/M phase interface and down-regulated the protein levels of cyclin A and B1, which are the major regulatory proteins at the G(2) to M transition of the cell cycle. Together, these results indicate that, in contrast to other EDs, 4-nonylphenol may exhibit a potent cytotoxicity through apoptosis via the caspase cascade and cell cycle arrest at the G(2)/M phase, and suggest that 4-nonylphenol may affect neurogenesis in the CNS.