长链非编码 RNA UCA1 通过调控 miR-495/Nrf2-ARE 信号通路抑制癫痫及其诱导的脑损伤。
LncRNA UCA1 inhibits epilepsy and seizure-induced brain injury by regulating miR-495/Nrf2-ARE signal pathway.
机构信息
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
出版信息
Int J Biochem Cell Biol. 2018 Jun;99:133-139. doi: 10.1016/j.biocel.2018.03.021. Epub 2018 Mar 30.
BACKGROUND
Both LncRNA UCA1 and miR-495 are crucial gene regulators in various disorders. This study aims to investigate their role in epilepsy and seizure-induced brain injury.
METHODS
In this research, rat model of epilepsy was established by pilocarpine induction. The RNA and protein expression in hippocampal tissues and neurons were determined by qRT-PCR and western blot, respectively. The hippocampal neurons were isolated from hippocampal tissues, and treated with magnesium-free (MGF) physiological solution for epileptiform activity induction. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Flow cytometry was used to analyze the cell apoptosis. Dual luciferase reporter assay was performed to determine the interaction between miR-495 and Nrf2 in HEK-293 cells.
RESULTS
The lncRNA UCA1 and Nrf2 were down-regulated in epileptiform hippocampal tissues and neurons, while the miR-495 was up-regulated. Over-expression of UCA1 inhibited apoptosis of hippocampal neurons by suppressing miR-495. MiR-495 negatively regulated Nrf2. UCA1 inhibited apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway. UCA1 suppressed pilocarpine-induced epilepsy in rat.
CONCLUSION
LncRNA UCA1 suppressed pilocarpine-induced epilepsy by inhibiting apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway, and thereby inhibiting brain injury induced by seizure.
背景
LncRNA UCA1 和 miR-495 都是各种疾病中重要的基因调控因子。本研究旨在探讨它们在癫痫和癫痫引起的脑损伤中的作用。
方法
本研究通过匹罗卡品诱导建立了大鼠癫痫模型。通过 qRT-PCR 和 Western blot 分别检测海马组织和神经元中的 RNA 和蛋白质表达。从海马组织中分离出海马神经元，并使用无镁（MGF）生理溶液处理以诱导癫痫样活动。通过重组质粒和细胞转染调节内源性相关基因的表达。使用流式细胞术分析细胞凋亡。双荧光素酶报告基因检测用于确定 HEK-293 细胞中 miR-495 和 Nrf2 之间的相互作用。
结果
在癫痫样海马组织和神经元中，lncRNA UCA1 和 Nrf2 下调，而 miR-495 上调。UCA1 的过表达通过抑制 miR-495 抑制海马神经元的凋亡。miR-495 负调控 Nrf2。UCA1 通过 miR-495/Nrf2-ARE 通路抑制海马神经元的凋亡。UCA1 抑制了匹罗卡品诱导的大鼠癫痫。
结论
LncRNA UCA1 通过 miR-495/Nrf2-ARE 通路抑制海马神经元的凋亡，从而抑制癫痫引起的脑损伤，抑制匹罗卡品诱导的癫痫。
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