miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia

被引：266

作者：

Yin, Ke-Jie ^{[1
]}

Deng, Zhen ^{[1
]}

Huang, Huarong ^{[1
]}

Hamblin, Milton ^{[1
]}

Xie, Changqing ^{[1
]}

Zhang, Jifeng ^{[1
]}

Chen, Y. Eugene ^{[1
]}

机构：

[1] Univ Michigan, Med Ctr, Dept Internal Med, Ctr Cardiovasc, Ann Arbor, MI 48109 USA

来源：

NEUROBIOLOGY OF DISEASE | 2010年 / 38卷 / 01期

基金：

美国国家卫生研究院;

关键词：

MicroRNAs; Apoptosis; bcl-2; bcl-w; Cerebral cortex; Oxygen-glucose deprivation; Cerebral ischemia; PROTEIN EXPRESSION; MICRORNA CLUSTER; BCL-2; GENE; APOPTOSIS; STROKE; OVEREXPRESSION; BIOGENESIS; TARGET; CANCER;

D O I：

10.1016/j.nbd.2009.12.021

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Dysfunction of the microRNA (miR) network has been emerging as a major regulator in neurological diseases. However, little is known about the functional significance of unique miRs in ischemic brain damage. Here, we found that miR-497 is induced in mouse brain after transient middle cerebral artery occlusion (MCAO) and mouse N2A neuroblastoma (N2A) cells after oxygen-glucose deprivation (OGD). Loss-of-miR-497 function significantly suppresses OGD-induced N2A cell death, whereas gain-of-miRA97 function aggravates OGD-induced neuronal loss. Moreover, miR-497 directly binds to the predicted 3'-UTR target sites of bcl-2/-w genes. Furthermore, knockdown of cerebral miR-497 effectively enhances bcl-2/-w protein levels in the ischemic region, attenuates ischemic brain infarction, and improves neurological outcomes in mice after focal cerebral ischemia. Taken together, our data suggest that miR-497 promotes ischemic neuronal death by negatively regulating antiapoptotic proteins, bcl-2 and bcl-w. We raise the possibility that this pathway may contribute to the pathogenesis of the ischemic brain injury in stroke. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：17 / 26

页数：10

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