MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress

Ping Liu; Haiping Zhao; Rongliang Wang; Peng Wang; Zhen Tao; Li Gao; Feng Yan; Xiangrong Liu; Shun Yu; Xunming Ji; Yumin Luo

doi:10.1161/STROKEAHA.114.007482

MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress

Stroke. 2015 Feb;46(2):513-9. doi: 10.1161/STROKEAHA.114.007482. Epub 2014 Dec 18.

Authors

Ping Liu¹, Haiping Zhao¹, Rongliang Wang¹, Peng Wang¹, Zhen Tao¹, Li Gao¹, Feng Yan¹, Xiangrong Liu¹, Shun Yu¹, Xunming Ji¹, Yumin Luo²

Affiliations

¹ From the Cerebrovascular Diseases Research Institute and Department of Neurology, Xuan Wu Hospital of Capital Medical University (P.L., H.Z., R.W., Z.T., L.G., F.Y., X.L., X.J., Y.L.); Beijing Institute for Brain Disorders, Beijing, China (X.J., Y.L.); Beijing Geriatric Medical Research Center (P.L., H.Z., R.W., Z.T., F.Y., X.L., X.J., Y.L.) and Key Laboratory of Neurodegenerative Diseases of Ministry of Education, and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases (P.L., H.Z., R.W., Z.T., F.Y., X.L., S.Y., X.J., Y.L.), Beijing, China; and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Department of Neurobiology, Liaoning Medical University, Jinzhou, China (P.W.).
² From the Cerebrovascular Diseases Research Institute and Department of Neurology, Xuan Wu Hospital of Capital Medical University (P.L., H.Z., R.W., Z.T., L.G., F.Y., X.L., X.J., Y.L.); Beijing Institute for Brain Disorders, Beijing, China (X.J., Y.L.); Beijing Geriatric Medical Research Center (P.L., H.Z., R.W., Z.T., F.Y., X.L., X.J., Y.L.) and Key Laboratory of Neurodegenerative Diseases of Ministry of Education, and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases (P.L., H.Z., R.W., Z.T., F.Y., X.L., S.Y., X.J., Y.L.), Beijing, China; and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Department of Neurobiology, Liaoning Medical University, Jinzhou, China (P.W.). yumin111@ccmu.edu.cn.

PMID: 25523055
DOI: 10.1161/STROKEAHA.114.007482

Abstract

Background and purpose: We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury.

Methods: Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H2O2 and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated.

Results: MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion. Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription factor nuclear factor erythroid 2-related factor. In neuronal cultures, miR-424 treatment abrogated H2O2-induced injury, as evidenced by decreased lactate dehydrogenase leakage and malondialdehyde level and increased cell viability and MnSOD activity; the protective effects of miR-424 against oxidative stress were reversed by nuclear factor erythroid 2-related factor knockdown and SOD inhibitor treatment.

Conclusions: MiR-424 protects against transient cerebral ischemia/reperfusion injury by inhibiting oxidative stress.

Keywords: MiR-424; ischemia-reperfusion injury; nuclear factor erythroid 2-related factor 2; oxidative stress; superoxide dismutase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Ischemia / metabolism*
Brain Ischemia / pathology
Brain Ischemia / prevention & control*
Cells, Cultured
Cerebral Cortex / metabolism
Cerebral Cortex / pathology
Male
Mice
Mice, Inbred C57BL
MicroRNAs / biosynthesis*
Oxidative Stress / physiology*
Reperfusion Injury / metabolism*
Reperfusion Injury / pathology
Reperfusion Injury / prevention & control*

Substances

MIRN424 microRNA, mouse
MicroRNAs