Fluoxetine Upregulates Phosphorylated-AKT and Phosphorylated-ERK1/2 Proteins in Neural Stem Cells: Evidence for a Crosstalk between AKT and ERK1/2 Pathways
Fluoxetine Upregulates Phosphorylated-AKT and Phosphorylated-ERK1/2 Proteins in Neural Stem Cells: Evidence for a Crosstalk between AKT and ERK1/2 Pathways
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氟西汀上调神经干细胞中的磷酸化 AKT 和磷酸化 ERK1/2 蛋白：AKT 和 ERK1/2 通路之间串扰的证据
DOI：
10.1007/s12031-012-9822-5
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发表时间：
2013-02-01
影响因子：
3.1
通讯作者：
Xie, Peng
中科院分区：
文献类型：
--
作者：
Huang, Wen;Zhao, Yu;Xie, Peng
氟西汀是一种广泛使用的抗抑郁药物，它可以抑制中枢神经系统（CNS）中血清素的再摄取。近年来的研究表明，氟西汀能促进神经发生，提高神经元存活率。然而，氟西汀是否调节神经干细胞（NSCs）的神经保护作用还有待阐明。在这项研究中，我们证明了50 μM氟西汀显著上调大鼠源性NSCs中磷酸化akt和ERK1/2蛋白的表达。此外，PI3-K抑制剂（LY294002）和MEK抑制剂（PD98059）均能有效阻断氟西汀处理的NSCs中磷酸化akt和磷酸化erk1 /2的表达（P< 0.05）。因此，我们得出结论，PI3K/AKT和MAPK/ERK通路之间的串扰涉及AKT和ERK1/2在氟西汀处理下的磷酸化。本研究指出了氟西汀作为抗抑郁药物在神经保护中的新作用，并揭示了两种信号通路之间的串扰机制。
Fluoxetine is a widely used antidepressant drug which inhibits the reuptake of serotonin in the central nervous system (CNS). Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the neuroprotection of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 50 μM fluoxetine significantly upregulated expression of the phosphorylated-AKT and ERK1/2 proteins in NSCs derived from rats. Besides, expression of phosphorylated-AKT and phosphorylated-ERK1/2 in fluoxetine-treated NSCs was effectively blocked (P< 0.05) by both PI3-K inhibitor (LY294002) and MEK inhibitor (PD98059). It was, therefore, concluded that the crosstalk between PI3K/AKT and MAPK/ERK pathways involved AKT and ERK1/2 phosphorylation by fluoxetine treatment. This study points to a novel role of fluoxetine in neuroprotection as an antidepressant drug and also unravels the crosstalk mechanism between the two signaling pathways.