Different effects of oxidative stress on activation of transcription factors in primary cultured rat neuronal and glial cells
Different effects of oxidative stress on activation of transcription factors in primary cultured rat neuronal and glial cells
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DOI：
10.1016/s0169-328x(97)00190-3
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发表时间：
1997-10-15
期刊：
影响因子：
--
通讯作者：
Ogawa, N
中科院分区：
文献类型：
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作者：
Iwata, E;Asanuma, M;Ogawa, N
我们分别使用台盼蓝排除法和电泳迁移率变动分析 (EMSA) 检查细胞活力以及转录因子 AP-1 和 CREB 的 DNA 结合活性的变化，比较了氧化应激对体外神经元和神经胶质细胞的细胞毒性作用。神经毒素 6-羟基多巴胺 (6-OHDA) 和 H2O2 以时间和浓度依赖性方式降低两种类型细胞的活力。两种神经毒素都会剂量依赖性地降低神经元细胞中的 DNA 结合活性。细胞活力测定的结果表明这些变化可能反映了神经元细胞活力的降低。相比之下，两种试剂都增加了神经胶质细胞中的 DNA 结合活性，尽管它们减少了细胞数量。这些结果表明氧化应激对神经元和神经胶质细胞中转录因子的影响是不同的。我们还研究了脑源性神经营养因子 (BDNF) 对 6-OHDA 或 H2O2 诱导的 DNA 结合活性变化的影响。在神经元细胞中，用 BDNF 预处理可防止 6-OHDA 或 H2O2 诱导的 DNA 结合活性降低。在神经胶质细胞中，6-OHDA 处理组中 BDNF 对氧化应激诱导的 DNA 结合活性变化的影响与 H2O2 处理组相反。我们的结果表明，6-OHDA 和 H2O2 可能通过不同的信号转导系统发挥其细胞毒性机制。 (C) 1997 Elsevier Science B.V.
We compared the cytotoxic effects of oxidative stress on neuronal and glial cells in vitro by examining the cell viability and changes in DNA-binding activities of transcription factors, AP-1 and CREB, using Trypan blue exclusion and electrophoretic mobility shift assay (EMSA), respectively. Neurotoxin 6-hydroxydopamine (6-OHDA) and H2O2 reduced the viability of both types of cells in time- and concentration-dependent manner. Both neurotoxins dose-dependently decreased DNA-binding activities in neuronal cells. The results of cell viability assay suggested that these changes may reflect the reduction in neuronal cell viability. In contrast, both reagents increased DNA-binding activities in glial cells, although they decreased cell numbers. These results suggest that the effects of oxidative stress on transcription factors is different in neuronal and glial cells. We also examined the effect of brain-derived neurotrophic factor (BDNF) on 6-OHDA- or H2O2-induced changes in DNA-binding activities. In neuronal cells, pre-treatment with BDNF prevented the decrease in DNA-binding activities induced by 6-OHDA or H2O2. In glial cells, the effect of BDNF on oxidative stress-induced changes in DNA-binding activities in the 6-OHDA-treated group were opposite to those in H2O2-treated group. Our results suggest that 6-OHDA and H2O2 may exert their cytotoxic mechanisms through different signal transduction systems. (C) 1997 Elsevier Science B.V.