DHA promotes the neuronal differentiation of rat neural stem cells transfected with GPR40 gene
DHA promotes the neuronal differentiation of rat neural stem cells transfected with GPR40 gene
复制标题
DHA促进转染GPR40基因的大鼠神经干细胞的神经元分化
DOI：
10.1016/j.brainres.2010.03.002
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发表时间：
2010-05-12
期刊：
影响因子：
2.9
通讯作者：
Zhou, Liangfu
中科院分区：
文献类型：
--
作者：
Ma, Dexuan;Zhang, Minmin;Zhou, Liangfu
G蛋白偶联受体40（GPR40）在人脑和胰腺中广泛表达，是七跨膜受体大家族的成员，可被多不饱和脂肪酸（PUFA），特别是二十二碳六烯酸（DHA）激活。近期研究表明，DHA/GPR40信号通路可能与海马体中的成年神经发生密切相关。在此，我们在培养的大鼠神经干细胞中构建表达GPR40基因的pEGFP - N1载体，证明了DHA诱导的成年大鼠干细胞的神经元分化、轴突生长和分支至少部分是通过GPR40介导的，并且即使在低浓度的DHA下仍然有效。此外，我们还发现DHA/GPR40诱导了PLC/IP3信号通路，从而调节细胞内钙离子的动员，且不受细胞外钙离子浓度的影响。这可能参与了转染GPR40基因的大鼠神经干细胞的神经元分化和轴突生长。这些数据为未来神经干细胞移植的应用提供了新的视角。（C）2010爱思唯尔公司。版权所有。
G-protein coupled receptor 40 (GPR40), which is expressed ubiquitously in the human brain and pancreas, is a member of the large family of seven-transmembrane receptors and can be activated by polyunsaturated fatty acid (PUFA), in particular docosahexaenoic acid (DHA). Recent studies have shown that the DHA/GPR40 signaling pathway may be closely related with adult neurogenesis in the hippocampus. Here, reconstructing pEGFP-N1 vector-expressing GPR40 gene in cultured rat neural stem cells, we demonstrated that DHA-induced neuronal differentiation, neurite growth and branching of adult rat stem cells is mediated at least in part through GPR40 and it remains effective even at low concentrations of DHA. Furthermore, we also revealed that DHA/GPR40 induced the PLC/IP3 signaling pathway and therefore modulated intracellular Ca2+ mobilization independent of extracellular Ca2+ concentration. This may be involved in neuronal differentiation and neurite growth in rat neural stem cells transfected with GPR40 gene. These data provide a new sight in the future utilization of neural stem cells transplantation. (C) 2010 Elsevier B.V. All rights reserved.