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Tetrachloro-1,4-benzoquinone induces apoptosis of mouse embryonic stem cells

Tetrachloro-1,4-benzoquinone induces apoptosis of mouse embryonic stem cells
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摘要 五氯苯酚(PCP ) 是普遍、坚持的环境沾染物,并且形成反应代谢物酶地被激活, tetrachloro-1,4-benzoquinone (TCBQ ) 。到我们的知识,胚胎的干细胞上的 TCBQ 毒性没有信息。这里,我们证明 TCBQ 显著地导致了老鼠的 apoptosis 以一种集中依赖者方式的胚胎的干细胞。我们也证明 TCBQ 由影响十提高了 genomic 5-hydroxymethylcytosine (5hmC )-- 在老鼠的十一 translocation (Tet ) dioxygenases 胚胎的干细胞。我们进一步调查了 Tet dioxygenases 是否在导致 TCBQ 的 apoptosis 被含有。由弄空所有三 dioxygenases (Tet1-3 ) ,我们发现 Tet dioxygenases 稍微禁止了 TCBQ 在低集中导致的早、迟了的 apoptosis (30   mol/L ) 。同时,在更高的集中由 TCBQ 对待(40 和 50   mol/L ) , apoptotic 房间的全部的百分比没被 Tet dioxygenases 影响。然而, Tet dioxygenases 趋于逮捕老鼠 ES 房间在早 apoptotic 舞台并且减少房间进入以后的 apoptotic 舞台。这些结果显示 Tet dioxygenases 在在老鼠塑造导致 TCBQ 的 apoptosis 起一个作用胚胎的干细胞。我们的学习提供新卓见进 PCP 和它的反应代谢物 TCBQ 的毒物学。 Pentachlorophenol(PCP) is a widespread,persistent environmental contaminant,and it is enzymatically activated to form a reactive metabolite,tetrachloro-l,4-benzoquinone(TCBQ).To our knowledge,there is no information about TCBQ toxicity on embryonic stem cells.Here,we demonstrated that TCBQ induced significantly apoptosis of mouse embryonic stem cells in a concentration-dependent manner.We also showed that TCBQ elevated genomic5-hydroxymethylcytosine(5hmC) by affecting ten-eleven translocation(Tet) dioxygenases in mouse embryonic stem cells.We further investigated whether Tet dioxygenases were implicated in TCBQ-induced apoptosis.By depleting all three dioxygenases(Tet1-3),we found that Tet dioxygenases slightly inhibited both early and late apoptosis induced by TCBQ at a low concentration(30 μmol/L).Meanwhile,treated by TCBQ at higher concentrations(40and 50 μmol/L),the total percentage of apoptotic cells was not affected by Tet dioxygenases.However,Tet dioxygenases tended to arrest mouse ES cells to be at early apoptotic stage and to reduce the cells to enter later apoptotic stage.These results indicate that Tet dioxygenases play a role in shaping TCBQ-induced apoptosis in mouse embryonic stem cells.Our study provides new insights into the toxicology of PCP and its reactive metabolite TCBQ.
作者 Cuiping Li Fengbang Wang Hailin Wang Li, Cuiping[1];Wang, Fengbang[1];Wang, Hailin[1]
出处 《环境科学学报:英文版》 SCIE EI CAS CSCD 2017年第1期5-12,共8页 Journal of Environmental Sciences
基金 supported by the National Natural Science Foundation of China(Nos.21327006,21435008,21321004) the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB14030200)
关键词 小鼠胚胎干细胞 细胞凋亡 诱导凋亡 苯醌 双加氧酶 活性代谢物 早期阶段 环境污染物 Tetrachloro-1,4-benzoquinone Ten-eleven translocation 5-Hydroxymethylcytosine Early apoptosis Late apoptosis
作者简介 E-mail: licuiping198585@126.com Corresponding author. E-mail: hlwang@rcees.ac.cn (Hailin Wang).
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