N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine attenuates oxygen-glucose deprivation and reoxygenation-induced cerebral ischemia-reperfusion injury via regulation of microRNAs

• Published in: Journal of integrative neuroscience 2020-06, Vol.19 (2), p.303-311
• Main Authors: Yang, Tiansong, Wang, Dongyan, Qu, Yuanyuan, Wang, Yulin, Feng, Yuenan, Yang, Yan, Luo, Qiang, Sun, Xiaowei, Yu, Guoqiang, He, Jia, Sun, Zhongren, Zhu, Yulan
• Format: Article
• Language: English
• Subjects: Amidines - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Basic-Leucine Zipper Transcription Factors - drug effects; Basic-Leucine Zipper Transcription Factors - metabolism; Cell Line, Tumor; Glucose - metabolism; Humans; Hypoxia - metabolism; MicroRNAs - drug effects; MicroRNAs - metabolism; oxygen-glucose deprivation|mirna-27a-5p|mirna-29b-3p|n-hydroxy-n'-(4-butyl-2-methylphenyl)-formamidine|bach 1|translational neuroscience; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism
• ISSN: 0219-6352; 1757-448X
• DOI: 10.31083/j.jin.2020.02.1236

Cerebral ischemia-reperfusion injury is a common complication that occurs during stroke treatment. Increasingly, microRNAs have been found to participate in the modulation of neuron function; however, the role of microRNAs in cerebral ischemia-reperfusion injury remains unclear. We developed a mechanism of cerebral ischemia-reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation-induced injury in human neuroblastoma SH-SY5Y cells. We found that treatment of oxygen-glucose deprivation and reoxygenation promoted the apoptosis of SH-SY5Y cells. Analysis of microRNAs sequencing revealed that the expression of microRNA-27a-5p was induced, and microRNA-29b-3p expression was inhibited in neuroblastoma cells exposed to oxygen-glucose deprivation and reoxygenation. Either inhibition of microRNA-27a-5p or overexpression of microRNA-29b-3p mitigated oxygen-glucose deprivation and reoxygenation-induced cellular apoptosis. Bach1 was authenticated as a target gene of microRNA-27a-5p. Also, microRNA-27a-5p mediated the expression of Bach 1 along with its downstream signaling. N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protected against oxygen-glucose deprivation and reoxygenation-induced apoptosis while decreasing miR-27a-5p expression and increasing microRNA-29b-3p expression. These results suggested that microRNA-27a-5p and microRNA-29b-3p may contribute to oxygen-glucose deprivation and reoxygenation-induced cellular injury. At the same time, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protects SH-SY5Y cells against oxygen-glucose deprivation and reoxygenation-induced injury partly through the inhibition of microRNA-27-a-5p and promotion of the Bach1/HO-1 signaling pathway.