MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2
Yu Tan,1,* Feng Zhou,2,* Dejiang Yang,1 Xiaowei Zhang,1 Meihong Zeng,1 Lei Wan1 1Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330008, People’s Republic of China; 2Department of Neurology, The Fifth Affiliated Hospital...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1afc7b39c33544ca87aa4a043d95f483 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1afc7b39c33544ca87aa4a043d95f483 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1afc7b39c33544ca87aa4a043d95f4832021-12-02T14:52:07ZMicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 21178-2021https://doaj.org/article/1afc7b39c33544ca87aa4a043d95f4832021-06-01T00:00:00Zhttps://www.dovepress.com/microrna-126a-5p-exerts-neuroprotective-effects-on-ischemic-stroke-via-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Yu Tan,1,* Feng Zhou,2,* Dejiang Yang,1 Xiaowei Zhang,1 Meihong Zeng,1 Lei Wan1 1Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330008, People’s Republic of China; 2Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong Province, 519000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu TanDepartment of Neurology, The Third Affiliated Hospital of Nanchang University, No. 128 Xiangshan Road, Nanchang City, Jiangxi Province, 330008, People’s Republic of ChinaEmail YuTanhospital@163.comBackground: Ischemic stroke is a destructive cerebrovascular disorder related to oxidative stress; NOX2 is a major source for ROS production; and miR-126a-5p is involved in several diseases, such as abdominal aortic aneurysm. We investigated the role of miR-126a-5p in regulating NOX2 in ischemic stroke.Methods: MiR-126a-5p and NOX2 were examined in the brains of rats subjected to cerebral ischemia/reperfusion (I/R) by RT-PCR and Western blot. MiR-126a-5p agomir was delivered to examine the effects of miR-126a-5p on I/R injury. The neurological deficit, infarct volume, and brain water content were evaluated. NOX activity, ROS production, and MDA and SOD levels were detected to assess oxidative stress. H&E staining was used to examine cell state. Apoptosis was evaluated by TUNEL, caspase-3 activity, and cleaved-caspase-3 protein level. The relationship between miR-126a-5p and NOX2 was analyzed by bioinformatics and luciferase reporter assay. MiR-126a-5p mimic, miR-126a-5p inhibitor, or pcDNA-NOX2 were transfected in SH-SY5Y cells to further assess the effects of miR-126a-5p on OGD/R-induced cells injury.Results: NOX2 was upregulated and miR-126a-5p was down-regulated in the brains of I/R rats. MiR-126a-5p agomir obviously reduced the neurological deficit, infarct volume, brain water content, oxidative stress, and apoptosis in I/R rats. MiR-126a-5p targeted NOX2 directly and regulated NOX2 negatively. Moreover, miR-126a-5p mimic elevated cell viability and inhibited oxidative stress and apoptosis in OGD/R-treated SH-SY5Y cells, while miR-126a-5p inhibitor had the opposite effects. NOX2 overexpression antagonized the protective effects of miR-126a-5p mimic on OGD/R-induced cell injury.Conclusion: MiR-126a-5p is a novel potential target for ischemic stroke therapy due to its protection against cerebral I/R injury via directly targeting NOX2.Keywords: oxidative stress, NOX2, miR-126a-5p, cerebral ischemia/reperfusionTan YZhou FYang DZhang XZeng MWan LDove Medical Pressarticleoxidative stressnox2mir-126a-5pcerebral ischemia/reperfusionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2089-2103 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
oxidative stress nox2 mir-126a-5p cerebral ischemia/reperfusion Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
| spellingShingle |
oxidative stress nox2 mir-126a-5p cerebral ischemia/reperfusion Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Tan Y Zhou F Yang D Zhang X Zeng M Wan L MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2 |
| description |
Yu Tan,1,* Feng Zhou,2,* Dejiang Yang,1 Xiaowei Zhang,1 Meihong Zeng,1 Lei Wan1 1Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330008, People’s Republic of China; 2Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong Province, 519000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu TanDepartment of Neurology, The Third Affiliated Hospital of Nanchang University, No. 128 Xiangshan Road, Nanchang City, Jiangxi Province, 330008, People’s Republic of ChinaEmail YuTanhospital@163.comBackground: Ischemic stroke is a destructive cerebrovascular disorder related to oxidative stress; NOX2 is a major source for ROS production; and miR-126a-5p is involved in several diseases, such as abdominal aortic aneurysm. We investigated the role of miR-126a-5p in regulating NOX2 in ischemic stroke.Methods: MiR-126a-5p and NOX2 were examined in the brains of rats subjected to cerebral ischemia/reperfusion (I/R) by RT-PCR and Western blot. MiR-126a-5p agomir was delivered to examine the effects of miR-126a-5p on I/R injury. The neurological deficit, infarct volume, and brain water content were evaluated. NOX activity, ROS production, and MDA and SOD levels were detected to assess oxidative stress. H&E staining was used to examine cell state. Apoptosis was evaluated by TUNEL, caspase-3 activity, and cleaved-caspase-3 protein level. The relationship between miR-126a-5p and NOX2 was analyzed by bioinformatics and luciferase reporter assay. MiR-126a-5p mimic, miR-126a-5p inhibitor, or pcDNA-NOX2 were transfected in SH-SY5Y cells to further assess the effects of miR-126a-5p on OGD/R-induced cells injury.Results: NOX2 was upregulated and miR-126a-5p was down-regulated in the brains of I/R rats. MiR-126a-5p agomir obviously reduced the neurological deficit, infarct volume, brain water content, oxidative stress, and apoptosis in I/R rats. MiR-126a-5p targeted NOX2 directly and regulated NOX2 negatively. Moreover, miR-126a-5p mimic elevated cell viability and inhibited oxidative stress and apoptosis in OGD/R-treated SH-SY5Y cells, while miR-126a-5p inhibitor had the opposite effects. NOX2 overexpression antagonized the protective effects of miR-126a-5p mimic on OGD/R-induced cell injury.Conclusion: MiR-126a-5p is a novel potential target for ischemic stroke therapy due to its protection against cerebral I/R injury via directly targeting NOX2.Keywords: oxidative stress, NOX2, miR-126a-5p, cerebral ischemia/reperfusion |
| format |
article |
| author |
Tan Y Zhou F Yang D Zhang X Zeng M Wan L |
| author_facet |
Tan Y Zhou F Yang D Zhang X Zeng M Wan L |
| author_sort |
Tan Y |
| title |
MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2 |
| title_short |
MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2 |
| title_full |
MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2 |
| title_fullStr |
MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2 |
| title_full_unstemmed |
MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2 |
| title_sort |
microrna-126a-5p exerts neuroprotective effects on ischemic stroke via targeting nadph oxidase 2 |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/1afc7b39c33544ca87aa4a043d95f483 |
| work_keys_str_mv |
AT tany microrna126a5pexertsneuroprotectiveeffectsonischemicstrokeviatargetingnadphoxidase2 AT zhouf microrna126a5pexertsneuroprotectiveeffectsonischemicstrokeviatargetingnadphoxidase2 AT yangd microrna126a5pexertsneuroprotectiveeffectsonischemicstrokeviatargetingnadphoxidase2 AT zhangx microrna126a5pexertsneuroprotectiveeffectsonischemicstrokeviatargetingnadphoxidase2 AT zengm microrna126a5pexertsneuroprotectiveeffectsonischemicstrokeviatargetingnadphoxidase2 AT wanl microrna126a5pexertsneuroprotectiveeffectsonischemicstrokeviatargetingnadphoxidase2 |
| _version_ |
1718389433793773568 |