MiR-124-5p/NOX2 Axis Modulates the ROS Production and the Inflammatory Microenvironment to Protect Against the Cerebral I/R Injury

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2020 Jan 18

PMID 31950451

Citations 27

Authors

Yakun Wu

Jia Yao

Kai Feng

Affiliations

Soon will be listed here.

Abstract

The reperfusion after an acute ischemic stroke can lead to a secondary injury, which is ischemia-reperfusion (I/R) injury. During ischemia, the reactive oxygen species (ROS) is over-produced, mostly from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). Besides, miRNAs are also associated with neuronal death in ischemic stroke. MiR-124-5p is selectively expressed within central nervous system (CNS) and is predicted to bind to NOX2 directly. Herein, we successfully set up cerebral I/R injury model in rats through middle cerebral artery occlusion (MCAO) surgery. After 12 h or 24 h of refusion, the superoxide dismutase (SOD) activity was significantly inhibited, accompanied by NOX2 protein increase within MCAO rat infarct area. In vitro, oxygen-glucose deprivation/refusion (OGD/R) stimulation on PC-12 cells significantly increased NOX2 protein levels, ROS production, and the cell apoptosis, while a significant suppression on SOD activity; OGD/R stimulation-induced changes in PC-12 cells described above could be significantly attenuated by NOX2 silence. In vivo, miR-124 overexpression improved, whereas miR-124 inhibition aggravated I/R injury in MCAO rats. miR-124-5p directly bound to the CYBB 3'-untranslated region (UTR) to negatively regulate CYBB expression and NOX2 protein level. In vitro, miR-124 overexpression improved, while NOX2 overexpression aggravated OGD/R-induced cellular injuries; NOX2 overexpression significantly attenuated the effects of miR-124 overexpression. Besides, miR-124 overexpression significantly repressed NF-κB signaling activation and TNFα and IL-6 production through regulating NOX2. In conclusion, miR-124-5p/NOX2 axis modulates NOX-mediated ROS production, the inflammatory microenvironment, subsequently the apoptosis of neurons, finally affecting the cerebral I/R injury.

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