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MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2

Authors :
Tan Y
Zhou F
Yang D
Zhang X
Zeng M
Wan L
Source :
Neuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2089-2103 (2021)
Publication Year :
2021
Publisher :
Dove Medical Press, 2021.

Abstract

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

Details

Language :
English
ISSN :
11782021
Volume :
ume 17
Database :
Directory of Open Access Journals
Journal :
Neuropsychiatric Disease and Treatment
Publication Type :
Academic Journal
Accession number :
edsdoj.1afc7b39c33544ca87aa4a043d95f483
Document Type :
article