期刊
NEUROBIOLOGY OF DISEASE
卷 38, 期 1, 页码 17-26出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.12.021
关键词
MicroRNAs; Apoptosis; bcl-2; bcl-w; Cerebral cortex; Oxygen-glucose deprivation; Cerebral ischemia
资金
- National Institutes of Health [HL68878, HL89544, HL92421, T32 HL007853]
- American Heart Association National Scientist Development [0630209N, 0835237N]
- American Heart Association [0840025N]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R21HL092421, R01HL068878, T32HL007853, R01HL089544] Funding Source: NIH RePORTER
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.
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