Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex.
Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex.
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DOI：
10.1038/jcbfm.2009.253
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发表时间：
2010-04
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影响因子：
--
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中科院分区：
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预处理描述了缺血刺激，其触发内源性神经保护反应，在随后的严重缺血损伤期间保护大脑，这种现象称为“耐受”。缺血耐受需要新的蛋白质合成，导致大脑对随后缺血的反应的基因组重编程，并且是短暂的。microRNAs（miRNAs）通过直接影响信使RNA（mRNA）的翻译来调节转录后基因的表达。我们检测了小鼠皮质对预处理、缺血性损伤和耐受的反应中的miRNA表达。我们的微阵列分析结果显示，miRNA表达在各组中一致改变，但预处理是miRNA的最重要调节因子。我们的生物信息学分析结果预测，预处理调节的miRNA最突出的目标是编码转录调节因子的mRNA;甲基-CpG结合蛋白2（MeCP 2）是最突出的目标。没有研究将MeCP 2与预处理或耐受联系起来，但调节MeCP 2表达的miR-132在预处理的皮质中减少。miR-132的下调与我们的发现一致，即缺血预处理诱导小鼠皮质中MeCP 2蛋白而不是mRNA的快速增加。这些研究揭示了缺血预处理调节小鼠大脑皮层中miRNAs及其预测靶点的表达，并进一步表明miRNAs和MeCP 2可以作为缺血预处理诱导的耐受的效应器。
Preconditioning describes the ischemic stimulus that triggers an endogenous, neuroprotective response that protects the brain during a subsequent severe ischemic injury, a phenomenon known as ‘tolerance’. Ischemic tolerance requires new protein synthesis, leads to genomic reprogramming of the brain’s response to subsequent ischemia, and is transient. MicroRNAs (miRNAs) regulate posttranscriptional gene expression by exerting direct effects on messenger RNA (mRNA) translation. We examined miRNA expression in mouse cortex in response to preconditioning, ischemic injury, and tolerance. The results of our microarray analysis revealed that miRNA expression is consistently altered within each group, but that preconditioning was the foremost regulator of miRNAs. Our bioinformatic analysis results predicted that preconditioning-regulated miRNAs most prominently target mRNAs that encode transcriptional regulators; methyl-CpG binding protein 2 (MeCP2) was the most prominent target. No studies have linked MeCP2 to preconditioning or tolerance, yet miR-132, which regulates MeCP2 expression, is decreased in preconditioned cortex. Downregulation of miR-132 is consistent with our finding that preconditioning ischemia induces a rapid increase in MeCP2 protein, but not mRNA, in mouse cortex. These studies reveal that ischemic preconditioning regulates expression of miRNAs and their predicted targets in mouse brain cortex, and further suggest that miRNAs and MeCP2 could serve as effectors of ischemic preconditioning-induced tolerance.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
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：
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影响因子：
25
作者：
Ballas, Nurit;Lioy, Daniel T.;Grunseich, Christopher;Mandel, Gail
通讯作者：
Mandel, Gail
DOI：
10.1097/00004647-199607000-00006
发表时间：
1996-07-01
影响因子：
6.3
作者：
Chen, J;Graham, SH;Simon, RP
通讯作者：
Simon, RP
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS