Melatonin promotes the acquisition of neural identity through extracellular-signal-regulated kinases 1/2 activation
Melatonin promotes the acquisition of neural identity through extracellular-signal-regulated kinases 1/2 activation
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褪黑激素通过细胞外信号调节激酶 1/2 激活促进神经同一性的获得
DOI：
10.1111/jpi.12153
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发表时间：
2014-09-01
影响因子：
10.3
通讯作者：
Hao, Aijun
中科院分区：
文献类型：
--
作者：
Chen, Xueran;Li, Xian;Hao, Aijun
褪黑激素是松果体的主要分泌产物，具有一系列生理和神经保护作用。然而，褪黑激素在确定神经身份的功能意义，以及这可能发生的机制，是未知的。在这项研究中，P19细胞被用作模型系统，并监测细胞行为。我们的数据表明，褪黑激素在决定神经定型过程中的细胞命运和促进多能性P19细胞（Oct 4（+）Sox 2（+））分化为神经干细胞（Oct 4（-）Sox 2（+））中起重要作用。这种促进作用似乎与MT 1受体的激活和细胞外信号调节激酶1/2（ERK 1/2）的磷酸化一致。此外，我们的研究结果表明，褪黑激素通过两种不同的机制调节P19细胞的神经命运规范：促进ERK 1/2的核定位和上调Sox 2的转录，并抑制Smad 1诱导的中胚层特异性基因，如Bra的表达。
Melatonin, a major pineal secretory product, exerts a range of physiological and neuroprotective effects. However, the functional significance of melatonin in determining neural identity, and the mechanisms by which this may occur, is unknown. In this study, P19 cells were used as a model system and cell behavior was monitored. Our data show that melatonin plays an important role in determining cell fate during neural commitment and promoting the differentiation of pluripotent P19 cells (Oct4(+) Sox2(+)) into neural stem cells (Oct4(-)Sox2(+)). This promotion appears to coincide with the activation of the MT1 receptor and phosphorylation of extracellular-signal-regulated kinases 1/2 (ERK1/2). Furthermore, our results show that melatonin regulates neural fate specification of P19 cells through two distinct mechanisms: the promotion of nuclear localization of ERK1/2 and upregulation of Sox2 transcription, and suppression of Smad1-induced expression of mesodermal-specific genes, such as Bra.