A Novel Mechanism of S-equol Action in Neurons and Astrocytes: The Possible Involvement of GPR30/GPER1
A Novel Mechanism of S-equol Action in Neurons and Astrocytes: The Possible Involvement of GPR30/GPER1
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DOI：
10.3390/ijms20205178
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发表时间：
2019-10-02
影响因子：
5.6
通讯作者：
Koibuchi, Noriyuki
中科院分区：
文献类型：
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作者：
Ariyani, Winda;Miyazaki, Wataru;Koibuchi, Noriyuki
S木酚是大豆异黄酮类大豆苷元的主要细菌代谢物。众所周知，它是一种植物雌激素，通过与核雌激素受体(ER)结合而发挥作用，ER在包括小脑在内的不同大脑区域表达。然而，S马儿对小脑发育和功能的影响尚未得到广泛研究。在这项研究中，用小鼠小脑原代培养、Neuro-2A克隆细胞和星形胶质细胞富集培养来评价S的作用。S水煎液可增强三碘甲腺原氨酸(T-3)诱导的浦肯野细胞的树突分枝和Neuro-2A细胞分化的突起生长。选择性G蛋白偶联ER(GPR30)拮抗剂G15和ER拮抗剂ICI 182,780均可抑制这种增强作用。另一方面，在星形胶质细胞中，S-乙醇诱导细胞增殖和细胞迁移，细胞外信号调节蛋白1/2磷酸化和F-肌动蛋白重排增加。这种影响被G15抑制，但不被ICI抑制。这些结果表明，S可能通过影响神经元和星形胶质细胞，包括GPR30和ER，从而促进小脑的发育。本文报道了S马儿促进小脑发育的新机制，为S马儿在发育中的应用提供了一种新的可能性。
S-equol is a major bacterial metabolite of the soy isoflavone daidzein. It is known to be a phytoestrogen that acts by binding to the nuclear estrogen receptors (ERs) that are expressed in various brain regions, including the cerebellum. However, the effects of S-equol on cerebellar development and function have not yet been extensively studied. In this study, the effects of S-equol were evaluated using a mouse primary cerebellar culture, Neuro-2A clonal cells, and an astrocyte-enriched culture. S-equol augmented the dendrite arborization of Purkinje cells induced by triiodothyronine (T-3) and the neurite growth of Neuro-2A cell differentiation. Such augmentation was suppressed by G15, a selective G-protein coupled ER (GPR30) antagonist, and ICI 182,780, an antagonist for ERs in both cultures. On the other hand, in astrocytes, S-equol induced cell proliferation and cell migration with an increase in the phosphorylated extracellular-signal-regulated kinase 1/2 and F-actin rearrangements. Such effects were suppressed by G15, but not by ICI. These findings indicated that S-equol may enhanced cerebellar development by affecting both neurons and astrocytes through several signaling pathways, including GPR30 and ERs. We here report a novel mechanism of S-equol in cerebellar development that may provide a novel possibility to use S-equol supplementation during development.