Silencing of miR-302b-3p alleviates isoflurane-induced neuronal injury by regulating PTEN expression and AKT pathway

被引:6
|
作者
Li, Linlin [1 ]
Lu, Shan [1 ]
Fan, Xiaodi [1 ]
机构
[1] Jilin Univ, China Japan Union Hosp, Dept Anesthesiol, 126 Xiantai St, Changchun 130033, Jilin, Peoples R China
关键词
miR-302b-3p; Isoflurane; Neuroprotection; PTEN; AKT; MEMORY IMPAIRMENT; EARLY EXPOSURE; DIFFERENTIATION; ANESTHESIA; ADULT; NEUROPROTECTION; NEUROGENESIS; PHOSPHATASE; INHIBITION; PERSISTENT;
D O I
10.1016/j.brainresbull.2020.12.016
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Isoflurane (ISO) is an anesthesia and can result in neuron injury. A previous study has indicated that microRNA-302b-3p (miR-302b-3p) exerts a crucial function in modulating cerebral ischemia/reperfusion damage-induced neuronal injury. We sought to examine the role of miR-302b-3p in ISO-induced neuronal injury. In the present study, the effects of miR-302b-3p on ISO-induced neuron injury were investigated by MTT and TUNEL assays. We discovered that ISO stimulation led to miR-302b-3p upregulation and neuronal injury. MiR-302b-3p silencing exerted protective effects against ISO induced neuronal injury. In addition, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was a direct downstream target gene of miR-302b-3p. MiR-302b-3p targets the 3'UTR of PTEN to inhibit its mRNA expression, and further reduces its protein expression. Silencing of PTEN partially reversed the protecting effects of silenced miR-302b-3p on ISO-induced injury of hippocampal neurons. Further, miR-302b-3p activated the AKT signaling pathway in neurons exposed to ISO by downregulation of PTEN. Finally, in vivo studies revealed that silencing of miR-302b-3p alleviates ISO-induced injury and spatial memory impairment of rats partly by upregulation of PTEN. Overall, our findings indicated that miR-302b-3p targets PTEN to activate the AKT pathway, and silencing of miR-302b-3p plays a neuroprotective role in ISO-induced neuronal injury by the PTEN/AKT pathway, suggesting miR-302b-3p as a crucial target for ISO-induced neuronal injury.
引用
收藏
页码:89 / 99
页数:11
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