Melatonin promotes neuroprotection of induced pluripotent stem cells-derived neural stem cells subjected to H2O2-induced injury in vitro

被引：11

作者：

Shu, Tao ^{[1
]}

Fan, Lei ^{[1
]}

Wu, Tao ^{[2
]}

Liu, Chang ^{[1
]}

He, Lei ^{[1
]}

Pang, Mao ^{[1
]}

Bu, Yang ^{[1
]}

Wang, Xuan ^{[1
]}

Wang, Juan ^{[3
]}

Rong, Limin ^{[1
]}

Liu, Bin ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Dept Spine Surg, Affiliated Hosp 3, Guangzhou 510630, Guangdong, Peoples R China

[2] Guangzhou Med Univ, Dept Emergency, Guangdong Prov Corps Hosp Chinese Peoples Armed P, Guangzhou 510000, Guangdong, Peoples R China

[3] Common Splendor Int Hlth Management, Dept Gynaecol, Guangzhou 510000, Guangdong, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2018年 / 825卷

基金：

中国博士后科学基金;

关键词：

Induced pluripotent stem cells; Neural stem cells; Melatonin; AKT; Reactive oxygen species; OXYGEN-GLUCOSE DEPRIVATION; FOCAL CEREBRAL-ISCHEMIA; SPINAL-CORD-INJURY; SIGNALING PATHWAY; HIPPOCAMPAL-NEURONS; FUNCTIONAL RECOVERY; BRAIN-INJURY; DIFFERENTIATION; RATS; ACTIVATION;

D O I：

10.1016/j.ejphar.2018.02.027

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 mu M H2O2, 1 mu M melatonin, 1 mu M melatonin receptor antagonist (Luzindole), or 10 mu M Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). The results showed that melatonin stimulated proliferation of iPSC-derived NSCs on H2O2 exposure. 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 H2O2 treatment. 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.

引用

页码：143 / 150

页数：8

共 39 条

[11] Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period [J].