Down-modulation of Bis sensitizes cell death in C6 glioma cells induced by oxygen-glucose deprivation
Down-modulation of Bis sensitizes cell death in C6 glioma cells induced by oxygen-glucose deprivation
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DOI：
10.1016/j.brainres.2010.06.043
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发表时间：
2010-08-19
期刊：
影响因子：
2.9
通讯作者：
Lee, Jeong-Hwa
中科院分区：
文献类型：
--
作者：
Jung, Seung Eun;Kim, Yong Kwan;Lee, Jeong-Hwa
Bcl-2相互作用细胞死亡抑制因子（Bis），也被称为Bag3，已参与抗应激和抗凋亡途径。在之前的研究中，我们观察到短暂性前脑缺血后大鼠海马反应性星形胶质细胞显著诱导Bis。为了研究这种诱导在缺血性损伤中的意义，我们在缺氧-葡萄糖剥夺（OGD）条件下，用siRNA降低C6胶质瘤细胞中Bis的表达。Bis敲除导致OGD后C6细胞死亡率升高，并伴有活性氧的积累。在细胞抗氧化剂中，用bis siRNA处理的细胞（bis-kd C6）显著干扰了超氧化物歧化酶（SOD）活性的诱导。Western blot结果显示，SOD1的表达在对照细胞中逐渐增加，而在OGD处理后的bis-kd细胞中没有观察到SOD1的表达。Sod1和Sod2转录本的定量分析表明，Sod1的诱导更明显地被Bis的减少所抑制。NF-kappa B作为Sod1基因的候选转录因子，在p65的核易位中测定了NF-kappa B的活性，表明NF-kappa B的活性在bis-kd C6中被减弱。在OGD条件下，Bis的过表达增加了NF-kappa B和Sod1 mRNA的激活，增加了细胞存活率。这些结果表明，体内缺血后反应性星形胶质细胞中Bis诱导的生理意义之一是保护胶质细胞免受氧化应激，可能是通过诱导SOD1，而SOD1与NF-kappa B.的激活有关(C) 2010 Elsevier B.V.。
Bcl-2 interacting cell death suppressor (Bis), also known as Bag3, has been implicated in anti-stress and anti-apoptotic pathways. In a previous study, we observed a significant induction of Bis in reactive astrocytes of the rat hippocampus after transient forebrain ischemia. To investigate the significance of this induction in ischemic injury, the expression of Bis was reduced with siRNA in C6 glioma cells and exposed to oxygen-glucose deprivation (OGD) conditions. Bis knock-down resulted in an increase in the cell death rate of the C6 cells after OGD, accompanied by accumulation of reactive oxygen species. Among the cellular antioxidants, the induction of superoxide dismutase (SOD) activity was significantly interfered within the cells treated with bis siRNA treated cells (bis-kd C6). A Western blot assay revealed that SOD1 expression gradually increased in control cells, which was not observed in bis-kd cells upon OGD treatment. A quantitative analysis of Sod1 and Sod2 transcripts indicated that the induction of Sod1 was more evidently suppressed by the reduction of Bis. As a transcription factor candidate for the Sod1 gene, the activity of NF-kappa B was determined the nuclear translocation of p65, showing that the activation of NF-kappa B was attenuated in bis-kd C6. Supporting this, an overexpression of Bis augments the activation of NF-kappa B and Sod1 mRNA with an increased cell survival under OGD conditions. These results suggest that one of physiological significances of Bis induction in reactive astrocytes after ischemia in vivo is to protect glial cells from oxidative stress, probably via the induction of SOD1, which is related to the activation of NF-kappa B. (C) 2010 Elsevier B.V. All rights reserved.