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

NEUROBIOLOGY OF DISEASE

卷:38

Article

Yin, Ke-Jie¹  Deng, Zhen¹  Huang, Huarong¹  Hamblin, Milton¹  Xie, Changqing¹  Zhang, Jifeng¹  Chen, Y. Eugene¹ 

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

关键词: MicroRNAs;    Apoptosis;    bcl-2;    bcl-w;    Cerebral cortex;    Oxygen-glucose deprivation;    Cerebral ischemia;   

DOI  :  10.1016/j.nbd.2009.12.021

来源: Elsevier

【 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.

【 授权许可】

Free