Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke
Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke
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DOI：
10.1016/j.expneurol.2008.03.017
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发表时间：
2008-07-01
影响因子：
5.3
通讯作者：
Kim, Seong Yun
中科院分区：
文献类型：
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作者：
Cho, Kyung-Ok;Kim, Young Sun;Kim, Seong Yun
唐氏综合征候选区域1 （DSCR1，也称为RCAN1或Adapt78）已被证明是由钙超载和氧化应激诱导的，这是缺血性疾病的致病标志。缺血性脑卒中后，炎症反应在神经元损失加重中起重要作用。在本研究中，我们研究了短暂性大脑中动脉闭塞（MCAO）后小鼠皮质中DSCR1的表达模式。然后，体外研究炎症介质是否能诱导DSCR1。雄性C57BL/6小鼠短暂MCAO 35 min，再灌注后6、24、72 h处死。DSCR1在梗死周围皮层第六层的表达于24 h开始增加，在短暂MCAO后72h显著增强。此外，实时逆转录聚合酶链反应和免疫组织化学显示，DSCR1亚型4 (DSCR1 -4) mRNA的诱导先于DSCR1蛋白的表达。在体外研究中，发现肿瘤坏死因子a和白细胞介素-1 β (IL-1 β)可诱导DSCR1-4 mRNA的强烈上调。此外，western blot分析显示，SK-N-SH神经母细胞瘤细胞中DSCR1-4的过表达减弱了il - β诱导的环氧化酶2和细胞间粘附分子I的表达。这些结果表明，瞬时MCAO后，小鼠梗死周围皮层中DSCR1表达上调。此外，我们的研究结果表明，炎症介质如TNF α和IL-1 β可以诱导DSCR1-4转录，这可能与炎症过程的缓解有关。(C) 2008爱思唯尔公司版权所有。
Down syndrome candidate region 1 (DSCR1; also known as RCAN1 or Adapt78) has been shown to be induced by calcium overload and oxidative stress which are included in the pathogenic hallmarks of the ischemic diseases. After ischemic stroke, inflammatory responses play an important role in the exacerbation of neuronal loss. In this Study, we investigated the expression pattern of DSCR1 in the mouse cortex after transient middle cerebral artery occlusion (MCAO). Then, in vitro studies were taken to address whether inflammatory mediators could induce DSCR1 Male C57BL/6 mice were subjected to transient MCAO for 35 min and sacrificed at 6, 24, and 72 h after the reperfusion. The expression of DSCR1 began to increase in layer VI of the peri-infarct cortex at 24 h and was prominently enhanced at 72h after transient MCAO. Moreover, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that the induction of the DSCR1 isoform 4 (DSCRI-4) mRNA preceded the expression of the DSCR1 protein. In in vitro studies, tumor necrosis factor a and interleukin-1 beta (IL-1 beta) were found to induce strong upregulation of DSCR1-4 mRNA. Furthermore, western blot analysis revealed that overexpression of DSCR1-4 in SK-N-SH neuroblastoma cells attenuated IL-beta-induced cyclooxygenase 2 and intercellular adhesion molecule I expression. These results demonstrate upregulation of DSCR1 in the mouse peri-infarct cortex following transient MCAO. In addition, our results suggest that inflammatory mediators such as TNF alpha and IL-1 beta can induce DSCR1-4 transcription, which may be associated with the alleviation of inflammatory processes. (C) 2008 Elsevier Inc. All rights reserved.