Yokota Y, Ohkubo H
Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
Exp Cell Res. 1996 Oct 10;228(1):1-7. doi: 10.1006/excr.1996.0291.
P19 mouse embryonal carcinoma cells differentiate into neurons and glial cells when treated with retinoic acid. In contrast, a subline of the P19 cells, RAC65, is known to show little sign of differentiation with the treatment. We treated the two embryonal carcinoma (EC) cell lines with 9-cis-retinoic acid and investigated its neuron-inducing activity. In P19 cells, 9-cis-retinoic acid showed an activity equal to that of all-trans-retinoic acid. However in RAC65 cells, 9-cis-retinoic acid induced neurons 10-fold more effectively than all-trans-retinoic acid. The order in which various retinoids appeared in P19 cells corresponded to that of retinoic acid receptors, and the order in RAC65 cells to that of retinoid X receptors (RXRs). Furthermore we found that the down-regulation of retinoid X receptor-gamma mRNA expression was associated with neuronal differentiation in both embryonal carcinoma cell lines. In addition, a synthetic RXR-selective retinoid induced neurons from both EC cells. Our findings support an intriguing possibility that the 9-cis-retinoic acid/retinoid X receptor system may play an important role in neural differentiation.
P19小鼠胚胎癌细胞在用视黄酸处理时会分化为神经元和神经胶质细胞。相比之下，已知P19细胞的一个亚系RAC65在该处理下几乎没有分化迹象。我们用9-顺式视黄酸处理这两种胚胎癌细胞系，并研究其诱导神经元的活性。在P19细胞中，9-顺式视黄酸显示出与全反式视黄酸相当的活性。然而在RAC65细胞中，9-顺式视黄酸诱导神经元的效率比全反式视黄酸高10倍。各种类视黄醇在P19细胞中出现的顺序与视黄酸受体的顺序相对应，在RAC65细胞中则与类视黄醇X受体（RXRs）的顺序相对应。此外，我们发现类视黄醇X受体γ mRNA表达的下调与两种胚胎癌细胞系中的神经元分化有关。另外，一种合成的RXR选择性类视黄醇能诱导两种胚胎癌细胞产生神经元。我们的研究结果支持了一种有趣的可能性，即9-顺式视黄酸/类视黄醇X受体系统可能在神经分化中起重要作用。
