Melatonin promotes neuroprotection of induced pluripotent stem cells-derived neural stem cells subjected to H2O2-induced injury in vitro.
Melatonin promotes neuroprotection of induced pluripotent stem cells-derived neural stem cells subjected to H2O2-induced injury in vitro.
复制标题
褪黑素可促进诱导多能干细胞衍生的神经干细胞在体外受到 H2O2 诱导损伤的神经保护作用。
DOI：
10.1016/j.ejphar.2018.02.027
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发表时间：
2018
影响因子：
5
通讯作者：
Rong Limin
中科院分区：
文献类型：
--
作者：
Shu Tao;Fan Lei;Wu Tao;Liu Chang;He Lei;Pang Mao;Bu Yang;Wang Xuan;Wang Juan;Liu Bin;Rong Limin
褪黑素是一种主要从松果体中提取的神经激素，具有神经保护作用。它具有抗氧化、抗炎和抗细胞凋亡的功能。然而，褪黑素对活性氧的作用机制尚不清楚。在这里，我们探讨褪黑素对暴露于过氧化氢（H2O2）的诱导多能干细胞（iPSC）来源的神经干细胞（NSCs）的潜在增殖和神经保护机制。用iPSCs诱导NSCs，然后用500 μM H2O2、1 μM褪黑素、1 μM褪黑素受体拮抗剂（Luzindole）或10 μM磷脂酰肌苷3激酶（PI3K）抑制剂（LY294002）预处理。结果表明，褪黑激素对暴露于h2o2的ipsc源性NSCs的增殖有促进作用。褪黑素还能显著改善线粒体膜电位的稳定，降低细胞凋亡率。用Luzindole或LY294002治疗可以抑制褪黑素对h2o2处理的ipsc源性NSCs的增殖和神经保护作用。我们的研究结果进一步表明，褪黑素的这些促进作用与AKT的磷酸化活性有关。因此，这些结果表明褪黑激素通过褪黑激素受体和PI3K/AKT信号通路介导ipsc源性NSCs免受h2o2诱导的损伤。
Melatonin is a neurohormone mainly extracted from the pineal gland with neuroprotective effects. It has antioxidant, anti-inflammatory, and antiapoptotic functions. However, the mechanism of melatonin against reactive oxygen species is unclear. Here, we explore the potential proliferative and neuroprotective mechanism of melatonin on induced pluripotent stem cells (iPSC)-derived neural stem cells (NSCs) exposed to hydrogen peroxide (H2O2). NSCs were induced from iPSCs, then pretreated with 500 μM H2O2, 1 μM melatonin, 1 μM melatonin receptor antagonist (Luzindole), or 10 μM Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). The results showed that melatonin stimulated proliferation of iPSC-derived NSCs on H2O2exposure. Melatonin also markedly improved stabilization of the mitochondrial membrane potential and reduced the rate of apoptosis. Treatment with Luzindole or LY294002 inhibited the increasing proliferative and neuroprotective effects of melatonin on iPSC-derived NSCs with H2O2treatment. Our results further demonstrated that these promotional effects of melatonin were related with the activity of phosphorylation of AKT. Therefore, these outcomes propose that melatonin protects iPSC-derived NSCs from H2O2-induced injury through the mediation of melatonin receptor and PI3K/AKT signaling pathway.