Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea.
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1526-30. doi: 10.1016/j.bbrc.2009.12.114. Epub 2009 Dec 28.
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 NaN(3) and 2-deoxy-d-glucose for 2h. 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.
虽然神经胶质细胞通过加剧神经元和非神经元细胞死亡在许多神经疾病的发病机制中起主要作用，但涉及的机制尚不清楚。我们研究了通过化学缺血获得的小胶质细胞（MCM）或星形胶质细胞（ACM）条件培养基对 SH-SY5Y 细胞神经元损伤的影响。化学缺血通过用NaN3和 2-脱氧-D-葡萄糖处理 2 小时来诱导。MCM 处理的 SH-SY5Y 细胞表现出活力降低、半胱天冬酶-3 活性增加、Bcl-2/Bax 比值降低、细胞色素 c 释放增加、炎症细胞因子增加和活性氧（ROS）生成增加。MCM 还增加了 gp91phox 烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶，该酶被 NADPH 氧化酶抑制剂 apocynin 和 gp91phox siRNA 抑制。然而，ACM 没有显示出任何显著变化。结果表明，由缺血性损伤激活的小胶质细胞可能通过激活 gp91phox NADPH 氧化酶增加活性氧的产生，从而导致神经元损伤。
