期刊
JOURNAL OF NEUROCHEMISTRY
卷 88, 期 6, 页码 1416-1423出版社
WILEY
DOI: 10.1046/j.1471-4159.2003.02270.x
关键词
apoptosis; cell cycle; central nervous system; endocrine disruptors; neural stem cells; 4-nonylphenol
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.
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