Ischemic pre-conditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways.
Ischemic pre-conditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways.
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DOI：
10.1111/j.1471-4159.2010.06735.x
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发表时间：
2010-06
影响因子：
4.7
通讯作者：
Vemuganti R
中科院分区：
文献类型：
--
作者：
Dharap A;Vemuganti R
已知脑基因表达受到亚致死性缺血事件（预处理; PC）的显著影响，亚致死性缺血事件诱导对未来损伤性缺血事件的耐受。小的非编码RNA被称为microRNA（miRNAs）最近被证明控制mRNA的翻译。我们目前分析了PC大鼠大脑皮层中的大脑miRNA。miRNA组反应迅速，在PC后6小时，51种miRNA的水平发生改变（26种上调，25种下调; >1.5倍变化）。其中20例甚至在PC后3天仍保持在改变的水平。与假手术相比，至少9种miRNA在PC后6小时至3天之间的一个或多个时间点显示>5倍的变化。生物信息学分析显示，2007个共同的靶点的miRNA的上调和459个共同的靶点的miRNA的下调后，PC。通路分析显示，MAP激酶和mTOR信号是PC后上调的miRNAs靶向的前2条KEGG通路，Wnt和GnRH信号是PC后下调的miRNAs靶向的前2条KEGG通路。我们推测miRNAs及其下游信号通路的改变可能在诱导缺血耐受中发挥作用。
Cerebral gene expression is known to be significantly influenced by a sublethal ischemic event (preconditioning; PC) that induces tolerance to future damaging ischemic events. Small non-coding RNAs known as microRNAs (miRNAs) were recently shown to control the mRNA translation. We currently profiled cerebral miRNAs in the cerebral cortex of rats subjected to PC. The miRNAome reacted quickly and by 6h following PC, levels of 51 miRNAs were altered (26 up- and 25 downregulated; >1.5 fold change). 20 of these stayed at the altered level even at 3 days after PC. At least 9 miRNAs showed >5 fold change at one or more time points between 6h to 3 days after PC compared to sham. Bioinformatics analysis showed 2007 common targets of the miRNAs that were up-regulated and 459 common targets of the miRNAs that were down-regulated after PC. Pathways analysis showed that MAP-kinase and mTOR signaling are the top 2 KEGG pathways targeted by the upregulated miRNAs, and Wnt and GnRH signaling are the top 2 KEGG pathways targeted by the down-regulated miRNAs after PC. We hypothesize that alterations in miRNAs and their down-stream mRNAs of signaling pathways might play a role in the induction of ischemic tolerance.
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DOI：
10.1038/jcbfm.2008.157
发表时间：
2009-04
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Arsham, AM;Howell, JJ;Simon, MC
通讯作者：
Simon, MC
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
4.7
作者：
Pradillo, Jesus M.;Fernandez-Lopez, David;Lizasoain, Ignacio
通讯作者：
Lizasoain, Ignacio
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C