Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase
Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase
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DOI：
10.1016/j.bbrc.2009.12.114
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发表时间：
2010-01-15
影响因子：
3.1
通讯作者：
Cho, Young-Wuk
中科院分区：
文献类型：
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作者：
Hur, Jinyoung;Lee, Pyeongjae;Cho, Young-Wuk
虽然神经胶质细胞通过加重神经细胞和非神经细胞的死亡在许多神经系统疾病的发病机制中发挥重要作用，但其机制尚不清楚。我们观察了小胶质细胞(MCM)或星形胶质细胞(ACM)条件培养液对SH-SY5Y细胞神经元损伤的影响。用NaN3和2-脱氧-D-葡萄糖处理SH-SY5Y细胞2 h，发现MCM处理的SH-SY5Y细胞存活率降低，caspase-3活性升高，Bcl2/Bax比值降低，细胞色素c释放增加，炎性细胞因子增多，活性氧(ROS)生成增加。MCM还可增加gp91Phox烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性。NADPH氧化酶抑制剂、apocynin和gp91Phox siRNA对其有抑制作用。然而，ACM没有表现出任何明显的变化。结果提示，缺血损伤所激活的小胶质细胞可能通过激活gp91Phox NADPH氧化酶而增加活性氧的产生，从而导致神经元损伤。(C)2009 Elsevier Inc.保留所有权利。
Although glial cells play a major role in the pathogenesis of many neurological diseases by exacerbating neuronal and non-neuronal cell death, the mechanisms involved are unclear. We examined the effects of microglia-(MCM) or astrocyte-(ACM) conditioned media obtained by chemical ischemia on the neuronal injury in SH-SY5Y cells. Chemical ischemia was induced by the treatment with NaN3 and 2-deoxy-D-glucose for 2 h. MCM-treated SH-SY5Y cells showed reduced the viability, increased caspase-3 activity, decreased Bcl-2/Bax ratio, and increased cytochrome c release, increased inflammatory cytokines, and increased reactive oxygen species (ROS) generation. MCM also increased gp91phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. which was inhibited by NADPH oxidase inhibitor, apocynin, and gp91phox siRNA. However, ACM did not show any significant changes. The results suggest that microglia activated by ischemic insult may increase reactive oxygen species generation via activation of gp91phox NADPH oxidase, resulting in neuronal injury. (c) 2009 Elsevier Inc. All rights reserved.