Abstract
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.
Highlights
Stroke is a disease characterized by ischemic and hemorrhagic brain injury
Flow cytometry analysis of FITC-annexin and PI dual-stains showed that the apoptosis percentage in SH-SY5Y cells exposed to OGD for 6 hours and reoxygenation for 24 hours increased from 9.5% to 32% versus the untreated group (Fig. 1C and 1D)
The caspase activity test related to the apoptosis pathway showed that the activity of caspase-3, caspase-8, and caspase-9 increased compared to the untreated group (Fig. 1E)
Summary
Stroke is a disease characterized by ischemic and hemorrhagic brain injury. Recombinant tissue plasminogen activator (rtPA) is recommended for the dissolution of the occluding thrombus and can be used to relieve the ischemic symptoms in patients (Xu et al, 2013). This treatment allows for a particular improvement in nerve function, it can cause more severe brain damage and dysfunction related to ischemia/reperfusion injury (Wechsler, 2011; Yellon and Hausenloy, 2007). Elucidation of the mechanisms underlying ischemia/reperfusion (I/R) may provide a novel therapeutic strategy for cerebral ischemia-reperfusion injury (IRI)
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