RAR and RXR selective ligands cooperatively induce apoptosis and neuronal differentiation in P19 embryonal carcinoma cells
RAR and RXR selective ligands cooperatively induce apoptosis and neuronal differentiation in P19 embryonal carcinoma cells
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DOI：
10.1096/fasebj.10.9.8801169
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发表时间：
1996-07-01
期刊：
影响因子：
4.8
通讯作者：
Ozato, K
中科院分区：
文献类型：
--
作者：
Horn, V;Minucci, S;Ozato, K
类维生素A引起胚胎癌（EC）细胞的分化，从而模拟哺乳动物发育中的事件。在此，我们表明类维生素A也引起P19 EC细胞的凋亡，在加入维甲酸（RA）后36小时内观察到特征性DNA片段化，对RA受体（RAR）具有选择性的合成类维生素A也有效诱导凋亡，而RXR选择性配体则没有作用，RAR和RXR配体的组合导致凋亡性细胞死亡的协同增加。与凋亡一样，RAR和RXR配体的组合协同诱导P19细胞的神经元分化。与RAR拮抗剂和P19细胞携带显性负RXR获得的数据表明，这两个过程是受体介导的，在一起，我们的研究结果表明，类维生素A诱导的细胞凋亡和神经元分化是密切相关的，RAR和RXR在这些过程中发挥作用，作为其各自的配体的活性受体。
Retinoids cause differentiation in embryonal carcinoma (EC) cells, thus mimicking events in mammalian development, Here, we show that retinoids also cause apoptosis in P19 EC cells, Characteristic DNA fragmentation was observed within 36 h after addition of retinoic acid (RA), Synthetic retinoids that are selective for RA receptors (RAR) were also effective in inducing apoptosis, whereas RXR selective ligands were without effect, The combination of RAR and RXR ligands resulted in a synergistic increase in apoptotic cell death, As with apoptosis, neuronal differentiation of P19 cells was synergistically induced by the combination of RAR and RXR ligands. Data obtained with an RAR antagonist and with P19 cells carrying a dominant negative RXR indicate that the two processes are receptor mediated, Together, our results indicate that retinoid-induced apoptosis and neuronal differentiation are closely coupled, and that both RAR and RXR play a role in these processes as active receptors for their respective ligands.