Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34
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DOI:
10.1016/j.jphs.2017.09.001
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发表时间:
2017-10-01
影响因子:
3.5
通讯作者:
Ishige, Kumiko
Ishige, Kumiko
中科院分区:
医学3区
文献类型:
--
作者:
Nango, Hiroshi;Kosuge, Yasuhiro;Ishige, Kumiko

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前列腺素E2(PGE 2)通过与E-前列腺素受体(EP 1 -4)结合发挥各种生物学作用。虽然最近的研究表明,PGE 2诱导一些神经元细胞,如小鼠DRG神经元和感觉神经元样ND 7/23细胞的细胞分化,但尚不清楚PGE 2是否在运动神经元的分化中发挥作用。在本研究中,我们研究了PGE 2诱导运动神经元分化的机制,使用NSC-34,一个小鼠运动神经元样细胞系。未分化的NSC-34细胞暴露于PGE 2和EP 2选择性激动剂布他前列素,导致MTT还原活性降低,而碘化丙啶阳性细胞的数量没有增加,神经突承载细胞的数量增加。EP 1/3激动剂Sulprostone也显著降低MTT还原活性20%;然而,在测试的浓度范围内未观察到神经突承载细胞数量的增加。PGE 2诱导的轴突生长在PF-0441848(一种EP 2选择性拮抗剂)的存在下显著减弱。用二丁酰-cAMP处理这些细胞增加了神经突承载细胞的数量,而对细胞增殖没有影响。这些结果表明,PGE 2通过激活EP 2亚型促进神经突起生长并抑制细胞增殖,并且cAMP信号通路参与PGE 2诱导的NSC-34细胞分化。(C)2017年,作者。Elsevier B. V.代表日本药理学会制作和主办。
Prostaglandin E2 (PGE2) exerts various biological effects by binding to E-prostanoid receptors (EP1-4). Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.